Parallel reactor with internal sensing

ABSTRACT

An apparatus and method for carrying out and monitoring the progress and properties of multiple reactions is disclosed. The method and apparatus are especially useful for synthesizing, screening, and characterizing combinatorial libraries, but also offer significant advantages over conventional experimental reactors as well. The apparatus generally includes multiple vessels for containing reaction mixtures, and systems for controlling the stirring rate and temperature of individual reaction mixtures or groups of reaction mixtures. In addition, the apparatus may include provisions for independently controlling pressure in each vessel, and a system for injecting liquids into the vessels at a pressure different than ambient pressure. In situ monitoring of individual reaction mixtures provides feedback for process controllers, and also provides data for determining reaction rates, product yields, and various properties of the reaction products, including viscosity and molecular weight.

RELATED APPLICATIONS

This application is a continuation in part of U.S. application Ser. No.09/177,170, filed Oct. 22, 1998, which claims the benefit of U.S.Provisional Application No. 60/096,603, filed Aug. 13, 1998.

BACKGROUND

1. Technical Field

The present invention relates to a method and apparatus for rapidlymaking, screening, and characterizing an array of materials in whichprocess conditions are controlled and monitored.

2. Discussion

In combinatorial chemistry, a large number of candidate materials arecreated from a relatively small set of precursors and subsequentlyevaluated for suitability for a particular application. As currentlypracticed, combinatorial chemistry permits scientists to systematicallyexplore the influence of structural variations in candidates bydramatically accelerating the rates at which they are created andevaluated. Compared to traditional discovery methods, combinatorialmethods sharply reduce the costs associated with preparing and screeningeach candidate.

Combinatorial chemistry has revolutionized the process of drugdiscovery. See, for example, 29 Acc. Chem. Res. 1-170 (1996); 97 Chem.Rev. 349-509 (1997); S. Borman, Chem. Eng. News 43-62 (Feb. 24, 1997);A. M. Thayer, Chem. Eng. News 57-64 (Feb. 12, 1996); N. Terret, 1 DrugDiscovery Today 402 (1996)). One can view drug discovery as a two-stepprocess: acquiring candidate compounds through laboratory synthesis orthrough natural products collection, followed by evaluation or screeningfor efficacy. Pharmaceutical researchers have long used high-throughputscreening (HTS) protocols to rapidly evaluate the therapeutic value ofnatural products and libraries of compounds synthesized and catalogedover many years. However, compared to HTS protocols, chemical synthesishas historically been a slow, arduous process. With the advent ofcombinatorial methods, scientists can now create large libraries oforganic molecules at a pace on par with HTS protocols.

Recently, combinatorial approaches have been used for discovery programsunrelated to drugs. For example, some researchers have recognized thatcombinatorial strategies also offer promise for the discovery ofinorganic compounds such as high-temperature superconductors,magnetoresistive materials, luminescent materials, and catalyticmaterials. See, for example, co-pending U.S. patent application Ser. No.08/327,513 “The Combinatorial Synthesis of Novel Materials” (publishedas WO 96/11878) and co-pending U.S. patent application Ser. No.08/898,715 “Combinatorial Synthesis and Analysis of OrganometallicCompounds and Catalysts” (published as WO 98/03251), which are bothherein incorporated by reference.

Because of its success in eliminating the synthesis bottleneck in drugdiscovery, many researchers have come to narrowly view combinatorialmethods as tools for creating structural diversity. Few researchers haveemphasized that, during synthesis, variations in temperature, pressure,ionic strength, and other process conditions can strongly influence theproperties of library members. For instance, reaction conditions areparticularly important in formulation chemistry, where one combines aset of components under different reaction conditions or concentrationsto determine their influence on product properties.

Moreover, because the performance criteria in materials science is oftendifferent than in pharmaceutical research, many workers have failed torealize that process variables often can be used to distinguish amonglibrary members both during and after synthesis. For example, theviscosity of reaction mixtures can be used to distinguish librarymembers based on their ability to catalyze a solution-phasepolymerization—at constant polymer concentration, the higher theviscosity of the solution, the greater the molecular weight of thepolymer formed. Furthermore, total heat liberated and/or peaktemperature observed during an exothermic reaction can be used to rankcatalysts.

Therefore, a need exists for an apparatus to prepare and screencombinatorial libraries in which one can monitor and control processconditions during synthesis and screening.

SUMMARY OF THE INVENTION

In accordance with one aspect of the present invention, there isprovided an apparatus for parallel processing of reaction mixtures. Theapparatus includes vessels sealed against fluid communication with oneanother and adapted for containing the reaction mixtures, a stirringsystem for agitating the reaction mixtures, and a temperature controlsystem for regulating the temperature of the reaction mixtures in thevessels. The apparatus also includes an injection system comprising afluid delivery probe movable from one vessel to another vessel foreffecting the introduction of a fluid into each of the vessels at apressure different than ambient pressure. The injection system isoperable for preventing leakage of fluid under pressure from each vesselduring the introduction of fluid by the fluid delivery probe and afterthe probe has moved to another vessel.

In one embodiment, the apparatus may consist of a monolithic reactorblock, which contains the vessels, or an assemblage of reactor blockmodules. A robotic material handling system can be used to automaticallyload the vessels with starting materials. In addition to heating orcooling individual vessels, the entire reactor block can be maintainedat a nearly uniform temperature by circulating a temperature-controlledthermal fluid through channels formed in the reactor block. The stirringsystem generally includes stirring members—blades, bars, and thelike—placed in each of the vessels, and a mechanical or magnetic drivemechanism. Torque and rotation rate can be controlled and monitoredthrough strain gages, phase lag measurements, and speed sensors.

The apparatus may optionally include a system for evaluating materialproperties of the reaction mixtures. The system includes mechanicaloscillators located within the vessels. When stimulated with avariable-frequency signal, the mechanical oscillators generate responsesignals that depend on properties of the reaction mixture. Throughcalibration, mechanical oscillators can be used to monitor molecularweight, specific gravity, elasticity, dielectric constant, conductivity,and other material properties of the reaction mixtures.

In accordance with a second aspect of the present invention, there isprovided an apparatus for monitoring rates of production or consumptionof a gas-phase component of a reaction mixture. The apparatus generallycomprises a closed vessel for containing the reaction mixture, astirring system, a temperature control system and a pressure controlsystem. The pressure control system includes a pressure sensor thatcommunicates with the vessel, as well as a valve that provides ventingof a gaseous product from the vessel. In addition, in cases where agas-phase reactant is consumed during reaction, the valve providesaccess to a source of the reactant. Pressure monitoring of the vessel,coupled with venting of product or filling with reactant allows theinvestigator to determine rates of production or consumption,respectively.

In accordance with a third aspect of the present invention, there isprovided an apparatus for monitoring rates of consumption of a gas-phasereactant. The apparatus generally comprises a closed vessel forcontaining the reaction mixture, a stirring system, a temperaturecontrol system and a pressure control system. The pressure controlsystem includes a pressure sensor that communicates with the vessel, aswell as a flow sensor that monitors the flow rate of reactant enteringthe vessel. Rates of consumption of the reactant can be determined fromthe reactant flow rate and filling time.

In accordance with a fourth aspect of the present invention, there isprovided a method of making and characterizing a plurality of materials.The method includes the steps of providing vessels with startingmaterials to form reaction mixtures, confining the reaction mixture ineach vessel against fluid communication with the other vessels and at apressure other than ambient pressure, and stirring the reaction mixturesfor at least a portion of the confining step. The method furtherincludes the step of evaluating the reaction mixtures by tracking atleast one characteristic of the reaction mixtures for at least a portionof the confining step. Various characteristics or properties can bemonitored during the evaluating step, including temperature, rate ofheat transfer, pressure, conversion of starting materials, rate ofconversion, torque at a given stirring rate, stall frequency, viscosity,molecular weight, specific gravity, elasticity, dielectric constant, andconductivity. The confining step further includes the step of injectinga fluid into at least one of the vessels.

In accordance with a fifth aspect of the present invention, there isprovided a method of monitoring the rate of consumption of a gas-phasereactant. The method comprises the steps of providing a vessel withstarting materials to form the reaction mixture, confining the reactionmixtures in the vessel to allow reaction to occur, and stirring thereaction mixture for at least a portion of the confining step. Themethod further includes filling the vessel with the gas-phase reactantuntil gas pressure in the vessel exceeds an upper-pressure limit, P_(H),and allowing gas pressure in the vessel to decay below a lower-pressurelimit, P_(L). Gas pressure in the vessel is monitored and recordedduring the addition and consumption of the reactant. This process isrepeated at least once, and rates of consumption of the gas-phasereactant in the reaction mixture are determined from the pressure versustime record.

In accordance with a sixth aspect of the present invention, there isprovided a method of monitoring the rate of production of a gas-phaseproduct. The method comprises the steps of providing a vessel withstarting materials to form the reaction mixture, confining the reactionmixtures in the vessel to allow reaction to occur, and stirring thereaction mixture for at least a portion of the confining step. Themethod also comprises the steps of allowing gas pressure in the vesselto rise above an upper-pressure limit, P_(H), and venting the vesseluntil gas pressure in the vessel falls below a lower-pressure limit,P_(L). The gas pressure in the vessel is monitored and recorded duringthe production of the gas-phase component and subsequent venting of thevessel. The process is repeated at least once, so rates of production ofthe gas-phase product can be calculated from the pressure versus timerecord.

In accordance with a seventh aspect of the present invention, there isprovided an apparatus for parallel processing of reaction mixturescomprising vessels for containing the reaction mixtures, a stirringsystem for agitating the reaction mixtures, a temperature control systemfor regulating the temperature of the reaction mixtures, and a fluidinjection system. The vessels are sealed to minimize unintentional gasflow into or out of the vessels, and the fluid injection system allowsintroduction of a liquid into the vessels at a pressure different thanambient pressure. The fluid injection system includes fill ports thatare adapted to receive a liquid delivery probe, such as a syringe orpipette, and also includes conduits, valves, and tubular injectors. Theconduits provide fluid communication between the fill ports and thevalves and between the valves and the injectors. The injectors arelocated in the vessels, and can have varying lengths, depending onwhether fluid injection is to occur in the reaction mixtures or in thevessel headspace above the reaction mixtures. Generally, a roboticmaterial handling system manipulates the liquid delivery probe andcontrols the valves.

In accordance with an eighth aspect of the present invention, there isprovided an apparatus for parallel processing of reaction mixturescomprising a reactor block having a series of wells therein extendingdown from an upper surface of the block, and an upper plate removablysecured to the reactor block over the upper surface thereof. The upperplate has openings therein in registry with the wells in the reactorblock. Removable liners are positioned in the wells for containing thereaction mixtures. A temperature control system is provided forregulating the temperature of the reaction mixtures. A stirring systemis attached to said upper plate and is removable with the upper platefor agitating the reaction mixtures. The stirring system comprisesspindles extending down into respective wells, each of the spindleshaving a first end and a second end, a stirring blade attached to thefirst end of each of the spindles, a drive mechanism located external tothe vessels that is adapted to rotate the spindles and magnetic feedthrough devices for magnetically coupling the drive mechanism to thesecond end of each of the spindles.

In one embodiment, the magnetic feed through device includes a rigidpressure barrier having a cylindrical interior surface that is openalong the base of the pressure barrier. The base of the pressure barrieris attached to the vessel so that the interior surface of the pressurebarrier and the vessel define a closed chamber. The magnetic feedthrough device further includes a magnetic driver that is rotatablymounted on the rigid pressure barrier and a magnetic follower that isrotatably mounted within the pressure barrier. The drive mechanism ismechanically coupled to the magnetic driver, and one end of the spindleis attached to a leg portion of the magnetic follower that extends intothe vessel headspace. Since the magnetic driver and follower aremagnetically coupled, rotation of the magnetic driver induces rotationof the magnetic follower and spindle.

In accordance with a ninth aspect of the present invention, there isprovided an apparatus for parallel processing of reaction mixturescomprising sealed vessels, a temperature control system, and a stirringsystem that includes multi-piece spindles that are partially containedin the vessels. Each of the spindles includes an upper spindle portionthat is mechanically coupled to a drive mechanism, and a stirrer of achemically resistant non-metal material removably attached to the upperspindle portion and contained in one of the vessels. In one embodiment,the removable stirrer is made of a chemically resistant plasticmaterial, such as polyethylethylketone or polytetrafluoroethylene, andis typically discarded after use.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a parallel reactor system in accordance with thepresent invention.

FIG. 2 shows a perspective view of a modular reactor block with arobotic liquid handling system.

FIG. 3 shows a temperature monitoring system.

FIG. 4 shows a cross-sectional view of an integral temperaturesensor-vessel assembly.

FIG. 5 shows a side view of an infrared temperature measurement system.

FIG. 6 shows a temperature monitoring and control system for a reactorvessel.

FIG. 7 illustrates another temperature control system, which includesliquid cooling and heating of the reactor block.

FIG. 8 is a cross-sectional view of thermoelectric devices sandwichedbetween a reactor block and heat transfer plate.

FIG. 9 is a cross-sectional view of a portion of a reactor block usefulfor obtaining calorimetric data.

FIG. 10 is an exploded perspective view of a stirring system for asingle module of a modular reactor block of the type shown in FIG. 2.

FIG. 11 is a schematic representation of an electromagnetic stirringsystem.

FIGS. 12-13 are schematic representations of portions of electromagnetstirring arrays in which the ratios of electromagnets to vessel sitesapproach 1:1 and 2:1, respectively, as the number of vessel sitesbecomes large.

FIG. 14 is a schematic representation of an electromagnet stirring arrayin which the ratio of electromagnets to vessel sites is 4:1.

FIG. 15 shows additional elements of an electromagnetic stirring system,including drive circuit and processor.

FIG. 16 illustrates the magnetic field direction of a 2×2 electromagnetarray at four different times during one rotation of a magnetic stirringbar.

FIG. 17 illustrates the magnetic field direction of a 4×4 electromagnetarray at five different times during one full rotation of a 3×3 array ofmagnetic stirring bars.

FIG. 18 illustrates the rotation direction of the 3×3 array of magneticstirring bars shown in FIG. 17.

FIG. 19 shows a wiring configuration for an electromagnetic stirringsystem.

FIG. 20 shows an alternate wiring configuration for an electromagneticstirring system.

FIG. 21 shows the phase relationship between sinusoidal source currents,I_(A)(t) and I_(B)(t), which drive two series of electromagnets shown inFIG. 19 and 20.

FIG. 22 is a block diagram of a power supply for an electromagneticstirring system.

FIG. 23 illustrates an apparatus for directly measuring the appliedtorque of a stirring system.

FIG. 24 shows placement of a strain gauge in a portion of a base platethat is similar to the lower plate of the reactor module shown in FIG.10.

FIG. 25 shows an inductive sensing coil system for detecting rotationand measuring phase angle of a magnetic stirring blade or bar.

FIG. 26 shows typical outputs from inductive sensing coils, whichillustrate phase lag associated with magnetic stirring for low and highviscosity solutions, respectively.

FIG. 27 illustrates how amplitude and phase angle will vary during areaction as the viscosity increases from a low value to a valuesufficient to stall the stirring bar.

FIGS. 28-29 show bending modes of tuning forks and bimorph/unimorphresonators, respectively.

FIG. 30 schematically shows a system for measuring the properties ofreaction mixtures using mechanical oscillators.

FIG. 31 shows an apparatus for assessing reaction kinetics based onmonitoring pressure changes due to production or consumption variousgases during reaction.

FIG. 32 shows results of calibration runs for polystyrene-toluenesolutions using mechanical oscillators.

FIG. 33 shows a calibration curve obtained by correlating M_(w) of thepolystyrene standards with the distance between the frequency responsecurve for toluene and each of the polystyrene solutions of FIG. 32.

FIG. 34 depicts the pressure recorded during solution polymerization ofethylene to polyethylene.

FIGS. 35-36 show ethylene consumption rate as a function of time, andthe mass of polyethylene formed as a function of ethylene consumed,respectively.

FIG. 37 shows a perspective view of an eight-vessel reactor module, ofthe type shown in FIG. 10, which is fitted with an optional fluidinjection system.

FIG. 38 shows a cross sectional view of a first embodiment of a fillport having an o-ring seal to minimize liquid leaks.

FIG. 39 shows a second embodiment of a fill port.

FIG. 40 shows a phantom front view of an injector manifold.

FIGS. 41-42 show a cross sectional view of an injector manifold alongfirst and second section lines shown in FIG. 40, respectively.

FIG. 43 shows a phantom top view of an injector adapter plate, whichserves as an interface between an injector manifold and a block of areactor module shown in FIG. 37.

FIG. 44 shows a cross sectional side view of an injector adapter platealong a section line shown in FIG. 43.

FIG. 45 shows an embodiment of a well injector.

FIG. 46 shows a top view of a reactor module.

FIGS. 47-48 shows “closed” and “open” states of an injector system valveprior to, and during, fluid injection, respectively.

FIG. 48 shows a stirring mechanism and associated seals for maintainingabove-ambient pressure in reactor vessels.

FIG. 49 shows a cross sectional view of a magnetic feed through stirringmechanism that helps minimize gas leaks associated with dynamic seals.

FIG. 50 shows a perspective view of a stirring mechanism shown in FIG.48, and provides details of a multi-piece spindle.

FIG. 51 shows details of a coupler portion of a multi-piece spindle.

FIG. 52 shows a cross section of the coupler of FIG. 51.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention provides an apparatus and method for carrying outand monitoring the progress and properties of multiple reactions. It isespecially useful for synthesizing, screening, and characterizingcombinatorial libraries, but offers significant advantages overconventional experimental reactors as well. For example, in situmonitoring of individual reaction mixtures not only provides feedbackfor process controllers, but also provides data for determining reactionrates, product yields, and various properties of the reaction products,including viscosity and molecular weight. Moreover, in situ monitoringcoupled with tight process control can improve product selectivity,provide opportunities for process and product optimization, allowprocessing of temperature-sensitive materials, and decrease experimentalvariability. Other advantages result from using small mixture volumes.In addition to conserving valuable reactants, decreasing sample sizeincreases surface area relative to volume within individual reactorvessels. This improves the uniformity of reaction mixtures, aidsgas-liquid exchange in multiphase reactions, and increases heat transferbetween the samples and the reactor vessels. Because large samplesrespond much slower to changes in system conditions, the use of smallsamples, along with in situ monitoring and process control, also allowsfor time-dependent processing and characterization.

Overview of Parallel Reactor

FIG. 1 shows one embodiment of a parallel reactor system 100. Thereactor system 100 includes removable vessels 102 for receivingreactants. Wells 104 formed into a reactor block 106 contain the vessels102. Although the wells 104 can serve as reactor vessels, removablevessels 102 or liners provide several advantages. For example, followingreaction and preliminary testing (screening), one can remove a subset ofvessels 102 from the reactor block 106 for further in-depthcharacterization. When using removable vessels 102, one can also selectvessels 102 made of material appropriate for a given set of reactants,products, and reaction conditions. Unlike the reactor block 106, whichrepresents a significant investment, the vessels 102 can be discarded ifdamaged after use. Finally, one can lower system 100 costs and ensurecompatibility with standardized sample preparation and testing equipmentby designing the reactor block 106 to accommodate commercially availablevessels.

As shown in FIG. 1, each of the vessels 102 contains a stirring blade108. In one embodiment, each stirring blade 108 rotates at about thesame speed, so that each of the reaction mixtures within the vessels 102experience similar mixing. Because reaction products can be influencedby mixing intensity, a uniform rotation rate ensures that anydifferences in products does not result from mixing variations. Inanother embodiment, the rotation rate of each stirring blade 108 can bevaried independently, which as discussed below, can be used tocharacterize the viscosity and molecular weight of the reaction productsor can be used to study the influence of mixing speed on reaction.

Depending on the nature of the starting materials, the types ofreactions, and the method used to characterize reaction products andrates of reaction, it may be desirable to enclose the reactor block 106in a chamber 110. The chamber 110 may be evacuated or filled with asuitable gas. In some cases, the chamber 110 may be used only during theloading of starting materials into the vessels 102 to minimizecontamination during sample preparation, for example, to preventpoisoning of oxygen sensitive catalysts. In other cases, the chamber 110may be used during the reaction process or the characterization phase,providing a convenient method of supplying one or more gases to all ofthe vessels 102 simultaneously. In this way, a gaseous reactant can beadded to all of the vessels 102 at one time. Note, however, it is oftennecessary to monitor the rate of disappearance of a gaseous reactant—forexample, when determining rates of conversion—and in such cases thevessels 102 are each sealed and individually connected to a gas source,as discussed below.

FIG. 2 shows a perspective view of a parallel reactor system 130comprised of a modular reactor block 132. The modular reactor block 132shown in FIG. 2 consists of six modules 134, and each module 134contains eight vessels (not shown). Note, however, the number of modules134 and the number of vessels within each of the modules 134 can vary.

The use of modules 134 offers several advantages over a monolithicreactor block. For example, the size of the reactor block 132 can beeasily adjusted depending on the number of reactants or the size of thecombinatorial library. Also, relatively small modules 134 are easier tohandle, transport, and fabricate than a single, large reactor block. Adamaged module can be quickly replaced by a spare module, whichminimizes repair costs and downtime. Finally, the use of modules 134improves control over reaction parameters. For instance, stirring speed,temperature, and pressure of each of the vessels can be varied betweenmodules.

In the embodiment shown in FIG. 2, each of the modules 134 is mounted ona base plate 136 having a front 138 and a rear 140. The modules 134 arecoupled to the base plate 136 using guides (not shown) that mate withchannels 142 located on the surface of the base plate 136. The guidesprevent lateral movement of the modules 134, but allow linear travelalong the channels 142 that extend from the front 138 toward the rear140 of the base plate 136. Stops 144 located in the channels 142 nearthe front 138 of the base plate 136 limit the travel of the modules 134.Thus, one or more of the modules 134 can be moved towards the front 138of the base plate 136 to gain access to individual vessels while theother modules 134 undergo robotic filling. In another embodiment, themodules 134 are rigidly mounted to the base plate 136 using bolts,clips, or other fasteners.

As illustrated in FIG. 2, a conventional robotic material handlingsystem 146 is ordinarily used to load vessels with starting materials.The robotic system 146 includes a pipette or probe 148 that dispensesmeasured amounts of liquids into each of the vessels. The robotic system146 manipulates the probe 148 using a 3-axis translation system 150. Theprobe 148 is connected to sources 152 of liquid reagents throughflexible tubing 154. Pumps 156, which are located along the flexibletubing 154, are used to transfer liquid reagents from the sources 152 tothe probe 148. Suitable pumps 156 include peristaltic pumps and syringepumps. A multi-port valve 158 located downstream of the pumps 156selects which liquid reagent from the sources 152 is sent to the probe148 for dispensing in the vessels.

The robotic liquid handling system 146 is controlled by a processor 160.In the embodiment shown in FIG. 2, the user first supplies the processor160 with operating parameters using a software interface. Typicaloperating parameters include the coordinates of each of the vessels andthe initial compositions of the reaction mixtures in individual vessels.The initial compositions can be specified as lists of liquid reagentsfrom each of the sources 152, or as incremental additions of variousliquid reagents relative to particular vessels.

Temperature Control and Monitoring

The ability to monitor and control the temperature of individual reactorvessels is an important aspect of the present invention. Duringsynthesis, temperature can have a profound effect on structure andproperties of reaction products. For example, in the synthesis oforganic molecules, yield and selectivity often depend strongly ontemperature. Similarly, in polymerization reactions, polymer structureand properties—molecular weight, particle size, monomer conversion,microstructure—an be influenced by reaction temperature. Duringscreening or characterization of combinatorial libraries, temperaturecontrol and monitoring of library members is often essential to makingmeaningful comparisons among members. Finally, temperature can be usedas a screening criteria or can be used to calculate useful process andproduct variables. For instance, catalysts of exothermic reactions canbe ranked based on peak reaction temperature and/or total heat releasedover the course of reaction, and temperature measurements can be used tocompute rates of reaction and conversion.

FIG. 3 illustrates one embodiment of a temperature monitoring system180, which includes temperature sensors 182 that are in thermal contactwith individual vessels 102. For clarity, we describe the temperaturemonitoring system 180 with reference to the monolithic reactor block 106of FIG. 1, but this disclosure applies equally well to the modularreactor block 132 of FIG. 2. Suitable temperature sensors 182 includejacketed or non-jacketed thermocouples (TC), resistance thermometricdevices (RTD), and thermistors. The temperature sensors 182 communicatewith a temperature monitor 184, which converts signals received from thetemperature sensors 182 to a standard temperature scale. An optionalprocessor 186 receives temperature data from the temperature monitor184. The processor 186 performs calculations on the data, which mayinclude wall corrections and simple comparisons between differentvessels 102, as well as more involved processing such as calorimetrycalculations discussed below. During an experimental run, temperaturedata is typically sent to storage 188 so that it can be retrieved at alater time for analysis.

FIG. 4 shows a cross-sectional view of an integral temperaturesensor-vessel assembly 200. The temperature sensor 202 is embedded inthe wall 204 of a reactor vessel 206. The surface 208 of the temperaturesensor 202 is located adjacent to the inner wall 210 of the vessel toensure good thermal contact between the contents of the vessel 206 andthe temperature sensor 202. The sensor arrangement shown in FIG. 3 isuseful when it is necessary to keep the contents of the reactor vessel206 free of obstructions. Such a need might arise, for example, whenusing a freestanding mixing device, such as a magnetic stirring bar.Note, however, that fabricating an integral temperature sensor such asthe one shown in FIG. 4 can be expensive and time consuming, especiallywhen using glass reactor vessels.

Thus, in another embodiment, the temperature sensor is immersed in thereaction mixture. Because the reaction environment within the vessel mayrapidly damage the temperature sensor, it is usually jacketed with aninert material, such as a fluorinated thermoplastic. In addition to lowcost, direct immersion offers other advantages, including rapid responseand improved accuracy. In still another embodiment, the temperaturesensor is placed on the outer surface 212 of the reactor vessel of FIG.4. As long as the thermal conductivity of the reactor vessel is known,relatively accurate and rapid temperature measurements can be made.

One can also remotely monitor temperature using an infrared systemillustrated in FIG. 5. The infrared monitoring system 230 comprises anoptional isolation chamber 232, which contains the reactor block 234 andvessels 236. The top 238 of the chamber 232 is fitted with a window 240that is transparent to infrared radiation. An infrared-sensitive camera242 positioned outside the isolation chamber 232, detects and recordsthe intensity of infrared radiation passing through the window 240.Since infrared emission intensity depends on source temperature, it canbe used to distinguish high temperature vessels from low temperaturevessels. With suitable calibration, infrared intensity can be convertedto temperature, so that at any given time, the camera 242 provides“snapshots” of temperature along the surface 244 of the reactor block234. In the embodiment shown in FIG. 5, the tops 246 of the vessels 236are open. In an alternate embodiment, the tops 246 of the vessels 236are fitted with infrared transparent caps (not shown). Note that, withstirring, the temperature is uniform within a particular vessel, andtherefore the surface temperature of the vessel measured by infraredemission will agree with the bulk temperature measured by a TC or RTDimmersed in the vessel.

The temperature of the reactor vessels and block can be controlled aswell as monitored. Depending on the application, each of the vessels canbe maintained at the same temperature or at different temperaturesduring an experiment. For example, one may screen compounds forcatalytic activity by first combining, in separate vessels, each of thecompounds with common starting materials; these mixtures are thenallowed to react at uniform temperature. One may then furthercharacterize a promising catalyst by combining it in numerous vesselswith the same starting materials used in the screening step. Themixtures then react at different temperatures to gauge the influence oftemperature on catalyst performance (speed, selectivity). In manyinstances, it may be necessary to change the temperature of the vesselsduring processing. For example, one may decrease the temperature of amixture undergoing a reversible exothermic reaction to maximizeconversion. Or, during a characterization step, one may ramp thetemperature of a reaction product to detect phase transitions (meltingrange, glass transition temperature). Finally, one may maintain thereactor block at a constant temperature, while monitoring temperaturechanges in the vessels during reaction to obtain calorimetric data asdescribed below.

FIG. 6 shows a useful temperature control system 260, which comprisesseparate heating 262 and temperature sensing 264 elements. The heatingelement 262 shown in FIG. 6 is a conventional thin filament resistanceheater whose heat output is proportional to the product of the filamentresistance and the square of the current passing through the filament.The heating element 262 is shown coiled around a reactor vessel 266 toensure uniform radial and axial heating of the vessel 266 contents. Thetemperature sensing element 264 can be a TC, RTD, and the like. Theheating element 262 communicates with a processor 268, which based oninformation received from the temperature sensor 264 through atemperature monitoring system 270, increases or decreases heat output ofthe heating element 262. A heater control system 272, located in thecommunication path between the heating element 262 and the processor268, converts a processor 268 signal for an increase (decrease) inheating into an increase (decrease) in electrical current through theheating element 262. Generally, each of the vessels 104 of the parallelreactor system 100 shown in FIG. 1 or FIG. 3 are equipped with a heatingelement 262 and one or more temperature sensors 264, which communicatewith a central heater control system 272, temperature monitoring system270, and processor 268, so that the temperature of the vessels 104 canbe controlled independently.

Other embodiments include placing the heating element 262 andtemperature sensor 264 within the vessel 266, which results in moreaccurate temperature monitoring and control of the vessel 266 contents,and combining the temperature sensor and heating element in a singlepackage. A thermistor is an example of a combined temperature sensor andheater, which can be used for both temperature monitoring and controlbecause its resistance depends on temperature.

FIG. 7 illustrates another temperature control system, which includesliquid cooling and heating of the reactor block 106. Regulating thetemperature of the reactor block 106 provides many advantages. Forexample, it is a simple way of maintaining nearly uniform temperature inall of the reactor vessels 102. Because of the large surface area of thevessels 102 relative to the volume of the reaction mixture, cooling thereactor block 106 also allows one to carryout highly exothermicreactions. When accompanied by temperature control of individual vessels102, active cooling of the reactor block 106 allows for processing atsub-ambient temperatures. Moreover, active heating or cooling of thereactor block 106 combined with temperature control of individualvessels 102 or groups of vessels 102 also decreases response time of thetemperature control feedback. One may control the temperature ofindividual vessels 102 or groups of vessels 102 using compact heattransfer devices, which include electric resistance heating elements orthermoelectric devices, as shown in FIG. 6 and FIG. 8, respectively.Although we describe reactor block cooling with reference to themonolithic reactor block 106, one may, in a like manner, independentlyheat or cool individual modules 134 of the modular reactor block 132shown in FIG. 2.

Returning to FIG. 7, a thermal fluid 290, such as water, steam, asilicone fluid, a fluorocarbon, and the like, is transported from auniform temperature reservoir 292 to the reactor block 106 using aconstant or variable speed pump 294. The thermal fluid 290 enters thereactor block 106 from a pump outlet conduit 296 through an inlet port298. From the inlet port 298, the thermal fluid 290 flows through apassageway 300 formed in the reactor block 106. The passageway maycomprise single or multiple channels. The passageway 300 shown in FIG.7, consists of a single channel that winds its way between rows ofvessels 102, eventually exiting the reactor block 106 at an outlet port302. The thermal fluid 290 returns to the reservoir 292 through areactor block outlet conduit 304. A heat pump 306 regulates thetemperature of the thermal fluid 290 in the reservoir 292 by adding orremoving heat through a heat transfer coil 308. In response to signalsfrom temperature sensors (not shown) located in the reactor block 106and the reservoir 292, a processor 310 adjusts the amount of heat addedto or removed from the thermal fluid 290 through the coil 308. To adjustthe flow rate of thermal fluid 290 through the passageway 300, theprocessor 310 communicates with a valve 312 located in a reservoiroutlet conduit 314. The reactor block 106, reservoir 292, pump 294, andconduits 296, 304, 314 can be insulated to improve temperature controlin the reactor block 106.

Because the reactor block 106 is typically made of a metal or othermaterial possessing high thermal conductivity, the single channelpassageway 300 is usually sufficient for maintaining the temperature ofthe block 106 a few degrees above or below room temperature. To improvetemperature uniformity within the reactor block 106, the passageway canbe split into parallel channels (not shown) immediately downstream ofthe inlet port 298. In contrast to the single channel passageway 300depicted in FIG. 7, each of the parallel channels passes between asingle row of vessels 102 before exiting the reactor block 106. Thisparallel flow arrangement decreases the temperature gradient between theinlet 298 and outlet 302 ports. To further improve temperatureuniformity and heat exchange between the vessels 102 and the block 106,the passageway 300 can be enlarged so that the wells 104 essentiallyproject into a cavity containing the thermal fluid 290. Additionally,one may eliminate the reactor block 106 entirely, and suspend or immersethe vessels 102 in a bath containing the thermal fluid 290.

FIG. 8 illustrates the use of thermoelectric devices for heating andcooling individual vessels. Thermoelectric devices can function as bothheaters and coolers by reversing the current flow through the device.Unlike resistive heaters, which convert electric power to heat,thermoelectric devices are heat pumps that exploit the Peltier effect totransfer heat from one face of the device to the other. A typicalthermoelectric assembly has the appearance of a sandwich, in which thefront face of the thermoelectric device is in thermal contact with theobject to be cooled (heated), and the back face of the device is inthermal contact with a heat sink (source). When the heat sink or sourceis ambient air, the back face of the device typically has an array ofthermally conductive fins to increase the heat transfer area.Preferably, the heat sink or source is a liquid. Compared to air,liquids have higher thermal conductivity and heat capacity, andtherefore should provide better heat transfer through the back face ofthe device. But, because thermoelectric devices are usually made withbare metal connections, they often must be physically isolated from theliquid heat sink or source.

For example, FIG. 8 illustrates one way of using thermoelectric devices330 to heat and cool reactor vessels 338 using a liquid heat sink orsource. In the configuration shown in FIG. 8, thermoelectric devices 330are sandwiched between a reactor block 334 and a heat transfer plate336. Reactor vessels 338 sit within wells 340 formed in the reactorblock 334. Thin walls 342 at the bottom of the wells 340, separate thevessels 338 from the thermoelectric devices 330, ensuring good thermalcontact. As shown in FIG. 8, each of the vessels 338 thermally contactsa single thermoelectric device 330, although in general, athermoelectric device can heat or cool more than one of the vessels 338.The thermoelectric devices 330 either obtain heat from, or dump heatinto, a thermal fluid that circulates through an interior cavity 344 ofthe heat transfer plate 336. The thermal fluid enters and leaves theheat transfer plate 336 through inlet 346 and outlet 348 ports, and itstemperature is controlled in a manner similar to that shown in FIG. 7.During an experiment, the temperature of the thermal fluid is typicallyheld constant, while the temperature of the vessels 338 is controlled byadjusting the electrical current, and hence, the heat transport throughthe thermoelectric devices 330. Though not shown in FIG. 8, thetemperature of the vessels 338 are controlled in a manner similar to thescheme depicted in FIG. 6. Temperature sensors located adjacent to thevessels 338 and within the heat transfer plate cavity 344 communicatewith a processor via a temperature monitor. In response to temperaturedata from the temperature monitor, the processor increases or decreaseheat flow to or from the thermoelectric devices 330. A thermoelectricdevice control system, located in the communication path between thethermoelectric devices 330 and the processor, adjusts the magnitude anddirection of the flow of electrical current through each of thethermoelectric devices 330 in response to signals from the processor.

Calorimetric Data Measurement and Use

Temperature measurements often provide a qualitative picture of reactionkinetics and conversion and therefore can be used to screen librarymembers. For example, rates of change of temperature with respect totime, as well as peak temperatures reached within each of the vesselscan be used to rank catalysts. Typically, the best catalysts of anexothermic reaction are those that, when combined with a set ofreactants, result in the greatest heat production in the shortest amountof time.

In addition to its use as a screening tool, temperaturemeasurement—combined with proper thermal management and design of thereactor system—can also be used to obtain quantitative calorimetricdata. From such data, scientists can, for example, compute instantaneousconversion and reaction rate, locate phase transitions (melting point,glass transition temperature) of reaction products, or measure latentheats to deduce structural information of polymeric materials, includingdegree of crystallinity and branching.

FIG. 9 shows a cross-sectional view of a portion of a reactor block 360that can be used to obtain accurate calorimetric data. Each of thevessels 362 contain stirring blades 364 to ensure that the contents 366of the vessels 362 are well mixed and that the temperature within anyone of the vessels 362, T_(j), is uniform. Each of the vessels 362contains a thermistor 368, which measures T_(j) and heats the vesselcontents 366. The walls 370 of the vessels 362 are made of glass,although one may use any material having relatively low thermalconductivity, and similar mechanical strength and chemical resistance.The vessels 362 are held within wells 372 formed in the reactor block360, and each of the wells 372 is lined with an insulating material 374to further decrease heat transfer to or from the vessels 362. Usefulinsulating materials 374 include glass wool, silicone rubber, and thelike. The insulating material 374 can be eliminated or replaced by athermal paste when better thermal contact between that reactor block 360and the vessels 362 is desired—good thermal contact is needed, forexample, when investigating exothermic reactions under isothermalconditions. The reactor block 360 is made of a material having highthermal conductivity, such as aluminum, stainless steel, brass, and soon. High thermal conductivity, accompanied by active heating or coolingusing any of the methods described above, help maintain uniformtemperature, T_(o), throughout the reactor block 360. One can accountfor non-uniform temperatures within the reactor block 360 by measuringT_(oj), the temperature of the block 360 in the vicinity of each of thevessels 362, using block temperature sensors 376. In such cases, T_(oj)instead of T_(o), is used in the calorimetric calculations describednext.

An energy balance around the contents 366 of one of the vessels 362 (jthvessel) yields an expression for fractional conversion, X_(j), of a keyreactant at any time, t, assuming that the heat of reaction, ΔH_(rj) andthe specific heat of the vessel contents 366, C_(pj), are known and areconstant over the temperature range of interest: $\begin{matrix}{{M_{j}c_{P,j}\frac{T_{j}}{t}} = {{m_{o,j}\Delta \quad H_{r,j}\frac{X_{j}}{t}} + Q_{{in},j} - {Q_{{out},j}.}}} & I\end{matrix}$

In expression I, M_(j) is the mass of the contents 366 of the jthvessel; m_(oj) is the initial mass of the key reactant; Q_(inj) is therate of heat transfer into the jth vessel by processes other thanreaction, as for example, by resistance heating of the thermistor 368.Q_(out,j) is the rate of heat transfer out of the jth vessel, which canbe determined from the expression:

Q_(out,j)=U_(j)A_(j)(T_(j)−T_(o))=U_(j)A_(j)ΔT_(j)  II

where A_(j) is the heat transfer area—the surface area of the jthvessel—and U_(j) is the heat transfer coefficient, which depends on theproperties of the vessel 362 and its contents 366, as well as thestirring rate. U_(j) can be determined by measuring the temperaturerise, ΔT_(j), in response to a known heat input.

Equations I and II can be used to determine conversion from calorimetricdata in at least two ways. In a first method, the temperature of thereactor block 360 is held constant, and sufficient heat is added to eachof the vessels 362 through the thermistor 368 to maintain a constantvalue of ΔT_(j). Under such conditions, and after combining equations Iand II, the conversion can be calculated from the expression$\begin{matrix}{{X_{j} = {\frac{1}{m_{o,j}\Delta \quad H_{r,j}}\left( {{U_{j}A_{j}t_{f}\Delta \quad T_{j}} - {\int_{0}^{t_{f}}{Q_{{in},j}\quad {t}}}} \right)}},} & {III}\end{matrix}$

where the integral can be determined by numerically integrating thepower consumption of the thermistor 368 over the length of theexperiment, t_(f). This method can be used to measure the heat output ofa reaction under isothermal conditions.

In a second method, the temperature of the reactor block 360 is againheld constant, but T_(j) increases or decreases in response to heatproduced or consumed in the reaction. Equation I and II become undersuch circumstances $\begin{matrix}{X_{j} = {\frac{1}{m_{o,j}\Delta \quad H_{r,j}}{\left( {{M_{j}{c_{P,j}\left( {T_{f,j} - T_{i,j}} \right)}} + {U_{j}A_{j}{\int_{0}^{t_{f}}{\Delta \quad T_{j}\quad {t}}}}} \right).}}} & {IV}\end{matrix}$

In equation IV, the integral can be determined numerically, and T_(fj)and T_(ij) are temperatures of the reaction mixture within the jthvessel at the beginning and end of reaction, respectively. Thus, ifT_(fj) equals T_(ij), the total heat liberated is proportional to∫₀^(t_(f))Δ  T_(j)  t.

This method is simpler to implement than the isothermal method since itdoes not require temperature control of individual vessels. But, it canbe used only when the temperature change in each of the reaction vessels362 due to reaction does not significantly influence the reaction understudy.

One may also calculate the instantaneous rate of disappearance of thekey reactant in the jth vessel, −r_(j), using equation I, III or IVsince −r_(j) is related to conversions through the relationship$\begin{matrix}{{{- r_{j}} = {C_{o,j}\frac{X_{j}}{t}}},} & V\end{matrix}$

which is valid for constant volume reactions. The constant C_(oj) is theinitial concentration of the key reactant.

Stirring Systems

Mixing variables such as stirring blade torque, rotation rate, andgeometry, may influence the course of a reaction and therefore affectthe properties of the reaction products. For example, the overall heattransfer coefficient and the rate of viscous dissipation within thereaction mixture may depend on the stirring blade rate of rotation.Thus, in many instances it is important that one monitor and control therate of stirring of each reaction mixture to ensure uniform mixing.Alternatively, the applied torque may be monitored in order to measurethe viscosity of the reaction mixture. As described in the next section,measurements of solution viscosity can be used to calculate the averagemolecular weight of polymeric reaction products.

FIG. 10 shows an exploded, perspective view of a stirring system for asingle module 390 of a modular reactor block of the type shown in FIG.2. The module 390 comprises a block 392 having eight wells 394 forcontaining removable reaction vessels 396. The number of wells 394 andreaction vessels 396 can vary. The top surface 398 of a removable lowerplate 400 serves as the base for each of the wells 394 and permitsremoval of the reaction vessels 396 through the bottom 402 of the block392. Screws 404 secure the lower plate 400 to the bottom 402 of theblock 392. An upper plate 406, which rests on the top 408 of the block392, supports and directs elongated stirrers 410 into the interior ofthe vessels 396. Each of the stirrers 410 comprises a spindle 412 and arotatable stirring member or stirring blade 414 which is attached to thelower end of each spindle 412. A gear 416 is attached to the upper endof each of each spindle 412. When assembled, each gear 416 meshes withan adjacent gear 416 forming a gear train (not shown) so that eachstirrer 410 rotates at the same speed. A DC stepper motor 418 providestorque for rotating the stirrers 410, although an air-driven motor, aconstant-speed AC motor, or a variable-speed AC motor can be usedinstead. A pair of driver gears 420 couple the motor 418 to the geartrain. A removable cover 422 provides access to the gear train, which issecured to the block 392 using threaded fasteners 424. In addition tothe gear train, one may employ belts, chains and sprockets, or otherdrive mechanisms. In alternate embodiments, each of the stirrers 410 arecoupled to separate motors so that the speed or torque of each of thestirrers 410 can be independently varied and monitored. Furthermore, thedrive mechanism—whether employing a single motor and gear train orindividual motors—can be mounted below the vessels 362. In such cases,magnetic stirring blades placed in the vessels 362 are coupled to thedrive mechanism using permanent magnets attached to gear train spindlesor motor shafts.

In addition to the stirring system, other elements shown in FIG. 10merit discussion. For example, the upper plate 406 may contain vesselseals 426 that allow processing at pressures different than atmosphericpressure. Moreover, the seals 426 permit one to monitor pressure in thevessels 396 over time. As discussed below, such information can be usedto calculate conversion of a gaseous reactant to a condensed species.Note that each spindle 412 may penetrate the seals 426, or may bemagnetically coupled to an upper spindle member (not shown) attached tothe gear 416. FIG. 10 also shows temperature sensors 428 embedded in theblock 392 adjacent to each of the wells 394. The sensors 428 are part ofthe temperature monitoring and control system described previously.

In another embodiment, an array of electromagnets rotate freestandingstirring members or magnetic stirring bars, which obviates the need forthe mechanical drive system shown in FIG. 10. Electromagnets areelectrical conductors that produce a magnetic field when an electriccurrent passes through them. Typically, the electrical conductor is awire coil wrapped around a solid core made of material having relativelyhigh permeability, such as soft iron or mild steel.

FIG. 11 is a schematic representation of one embodiment of anelectromagnet stirring array 440. The electromagnets 442 or coilsbelonging to the array 440 are mounted in the lower plate 400 of thereactor module 390 of FIG. 10 so that their axes are about parallel tothe centerlines of the vessels 396. Although greater magnetic fieldstrength can be achieved by mounting the electromagnets with their axesperpendicular to the centerlines of the vessels 396, such a design ismore difficult to implement since it requires placing electromagnetsbetween the vessels 396. The eight crosses or vessel sites 444 in FIG.11 mark the approximate locations of the respective centers of each ofthe vessels 396 of FIG. 10 and denote the approximate position of therotation axes of the magnetic stirring bars (not shown). In the array440 shown in FIG. 11, four electromagnets 442 surround each vessel site444, though one may use fewer or greater numbers of electromagnets 442.The minimum number of electromagnets per vessel site is two, but in sucha system it is difficult to initiate stirring, and it is common to stallthe stirring bar. Electromagnet size and available packing densityprimarily limit the maximum number of electromagnets.

As illustrated in FIG. 11, each vessel site 444, except those at theends 446 of the array 440, shares its four electromagnets 442 with twoadjacent vessel sites. Because of this sharing, magnetic stirring barsat adjacent vessel sites rotate in opposite directions, as indicated bythe curved arrows 448 in FIG. 11, which may lead to stalling. Otherarray configurations are possible. For example, FIG. 12 shows a portionof an array 460 in which the ratio of electromagnets 462 to vessel sites464 approaches 1:1 as the number of vessel sites 464 becomes large.Because each of the vessel sites 464 shares its electromagnets 462 withits neighbors, magnetic stirring bars at adjacent vessel sites rotate inopposite directions, as shown by curved arrows 466. In contrast, FIG. 13shows a portion of an array 470 in which the ratio of electromagnets 472to vessel sites 474 approaches 2:1 as the number of vessel sites becomeslarge. Because of the comparatively large number of electromagnets 472to vessel sites 474, all of the magnetic stirring bars can be made torotate in the same direction 476, which minimizes stalling. Similarly,FIG. 14 shows an array 480 in which the number of electromagnets 482 tovessel sites 484 is 4:1. Each magnetic stirring bar rotates in the samedirection 486.

FIG. 15 illustrates additional elements of an electromagnetic stirringsystem 500. For clarity, FIG. 15 shows a square electromagnet array 502comprised of four electromagnets 504, although larger arrays, such asthose shown in FIG. 12-14, can be used. Each of the electromagnets 504comprises a wire 506 wrapped around a high permeability solid core 508.The pairs of electromagnets 504 located on the two diagonals of thesquare array 502 are connected in series to form a first circuit 510 anda second circuit 512. The first 510 and second 512 circuits areconnected to a drive circuit 514, which is controlled by a processor516. Electrical current, whether pulsed or sinusoidal, can be variedindependently in the two circuits 510, 512 by the drive circuit 514 andprocessor 516. Note that within each circuit 510, 512, the current flowsin opposite directions in the wire 506 around the core 508. In this way,each of the electromagnets 504 within a particular circuit 510, 512 haveopposite magnetic polarities. The axes 518 of the electromagnets 504 areabout parallel to the centerline 520 of the reactor vessel 522. Amagnetic stirring bar 524 rests on the bottom of the vessel 522 prior tooperation. Although the electromagnets 504 can also be oriented withtheir axes 518 perpendicular to the vessel centerline 520, the parallelalignment provides higher packing density.

FIG. 16 shows the magnetic field direction of a 2×2 electromagnet arrayat four different times during one full rotation of the magneticstirring bar 524 of FIG. 15, which is rotating at a steady frequency ofω radians·s⁻¹. In FIG. 16, a circle with a plus sign 532 indicates thatthe electromagnet produces a magnetic field in a first direction; acircle with a minus sign 534 indicates that the electromagnet produces amagnetic field in a direction opposite to the first direction; and acircle with no sign 536 indicates that the electromagnet produces nomagnetic field. At time t=0, the electromagnets 530 produce an overallmagnetic field with a direction represented by a first arrow 538 at thevessel site. At time ${t = \frac{\pi}{2\omega}},$

the electromagnets 540 produce an overall magnetic field with adirection represented by a second arrow 542. Since the magnetic stirringbar 524 (FIG. 15) attempts to align itself with the direction of theoverall magnetic field, it rotates clockwise ninety degrees from thefirst direction 538 to the second direction 542. At time${t = \frac{\pi}{\omega}},$

the electromagnets 544 produce an overall magnetic field with adirection represented by a third arrow 546. Again, the magnetic stirringbar 524 aligns itself with the direction of the overall magnetic field,and rotates clockwise an additional ninety degrees. At time${t = \frac{3\pi}{2\omega}},$

the electromagnets 548 produce an overall magnetic field with adirection represented by a fourth arrow 550, which rotates the magneticstirring bar 524 clockwise another ninety degrees. Finally, at time${t = \frac{2\pi}{\omega}},$

the electromagnets 530 produce an overall magnetic field with directionrepresented by the first arrow 538, which rotates the magnetic stirringbar 524 back to its position at time t=0.

FIG. 17 illustrates magnetic field direction of a 4×4 electromagneticarray at five different times during one full rotation of a 3×3 array ofmagnetic stirring bars. As in FIG. 15, a circle with a plus sign 570, aminus sign 572, or no sign 574 represents the magnetic field directionof an individual electromagnet, while an arrow 576 represents thedirection of the overall magnetic field at a vessel site. As shown,sixteen electromagnets are needed to rotate nine magnetic stirring bars.But, as indicated in FIG. 18, due to sharing of electromagnets bymultiple magnetic stirring bars, the rotational direction of themagnetic fields is non-uniform. Thus, five of the fields rotate in aclockwise direction 590 while the remaining four fields rotate in acounter-clockwise direction 592.

FIG. 19 and FIG. 20 illustrate wiring configurations for electromagnetarrays in which each vessel site is located between four electromagnetsdefining four corners of a quadrilateral sub-array. For each vesselsite, both wiring configurations result in an electrical connectionbetween electromagnets located on the diagonals of a given sub-array. Inthe wiring configuration 610 shown in FIG. 19, electromagnets 612 inalternating diagonal rows are wired together to form two series ofelectromagnets 612. Dashed and solid lines represent electricalconnections between electromagnets 612 in a first series 614 and asecond series 616, respectively. Plus signs 618 and minus signs 620indicate polarity (magnetic field direction) of individualelectromagnets 612 at any time, t, when current in the first series 614and the second series 616 of electromagnets 612 are in phase. FIG. 20illustrates an alternate wiring configuration 630 of electromagnets 632,where again, dashed and solid lines represent electrical connectionsbetween the first 634 and second series 636 of electromagnets 632, andplus signs 638 and minus signs 640 indicate magnetic polarity.

Note that for both wiring configurations 610, 630, the polarities of theelectromagnets 612, 632 of the first series 614, 634 are not the same,though amplitudes of the current passing through the connections betweenthe electromagnets 612, 632 of the first series 614, 634 are equivalent.The same is true for the second series 616, 636 of electromagnets 612,632. One can achieve opposite polarities within the first series 614,634 or second series 616, 636 of electromagnets 612, 632 by reversingthe direction of electrical current around the core of the electromagnet612, 632. See, for example, FIG. 15. In the two wiring configurations610, 630 of FIGS. 19 and 20, every quadrilateral array of four adjacentelectromagnets 612, 632 defines a site for rotating a magnetic stirringbar, and the diagonal members of each of the four adjacentelectromagnets 612, 632 belong to the first series 614, 634 and thesecond 616, 636 series of electromagnets 612, 632. Moreover, within anyset of four adjacent electromagnets 612, 632, each pair ofelectromagnets 612, 632 belonging to the same series have oppositepolarities. The two wiring configurations 610, 630 of FIGS. 19 and 20can be used with any of the arrays 460, 470, 480 shown in FIGS. 12-14.

The complex wiring configurations 610, 630 of FIGS. 19 and 20 can beplaced on a printed circuit board, which serves as both a mechanicalsupport and alignment fixture for the electromagnets 612, 632. The useof a printed circuit board allows for rapid interconnection of theelectromagnets 612, 632, greatly reducing assembly time and cost, andeliminating wiring errors associated with manual soldering of hundredsof individual connections. Switches can be used to turn stirring on andoff for individual rows of vessels. A separate drive circuit may be usedfor each row of vessels, which allows stirring speed to be used as avariable during an experiment.

FIG. 21 is a plot 650 of current versus time and shows the phaserelationship between sinusoidal source currents, I_(A)(t) 652 andI_(B)(t) 654, which drive, respectively, the first series 614, 634 andthe second series 616, 636 of electromagnets 612, 632 shown in FIGS. 19and 20. The two source currents 652, 654 have equivalent peak amplitudeand frequency, ω_(D), though I_(A)(t) 652 lags I_(B)(t) 654 by {fraction(π/2)} radians. Because of this phase relationship, magnetic stirringbars placed at rotation sites defined by any four adjacentelectromagnets 612, 632 of FIGS. 19 and 20 will each rotate at anangular frequency of ω_(D), though adjacent stirring bars will rotate inopposite directions when the electromagnet array 460 depicted in FIG. 12is used. If, however, the arrays 470, 480 shown in FIGS. 13 and 14 areused, adjacent stirring bars will rotate in the same direction. In analternate embodiment, a digital approximation to a sine wave can beused.

FIG. 22 is a block diagram of a power supply 670 for an electromagnetarray 672. Individual electromagnets 674 are wired together in a firstand second series as, for example, shown in FIGS. 19 or 20. The firstand second series of electromagnets 674 are connected to a power source676, which provides the two series with sinusoidal driving currents thatare {fraction (π/2)} radians out of phase. Normally, the amplitudes ofthe two driving currents are the same and do not depend on frequency. Aprocessor 678 controls both the amplitude and the frequency of thedriving currents.

Viscosity and Related Measurements

The present invention provides for in situ measurement of viscosity andrelated properties. As discussed below, such data can be used, forexample, to monitor reactant conversion, and to rank or characterizematerials based on molecular weight or particle size.

The viscosity of a polymer solution depends on the molecular weight ofthe polymer and its concentration in solution. For polymerconcentrations well below the “semidilute limit”—the concentration atwhich the solvated polymers begin to overlap one another—the solutionviscosity, η, is related to the polymer concentration, C, in the limitas C approaches zero by the expression

η=(1+C[η])η_(s)  VI

where η_(s) is the viscosity of the solvent. Essentially, adding polymerto a solvent increases the solvent's viscosity by an amount proportionalto the polymer concentration. The proportionality constant [η], is knownas the intrinsic viscosity, and is related to the polymer molecularweight, M, through the expression

 [η]=[η_(o)]M^(α),  VI

where [η_(o)] and a are empirical constants. Equation VII is known asthe Mark-Houwink-Sakurda (MHS) relation, and it, along with equation VI,can be used to determine molecular weight from viscosity measurements.

Equation VI requires concentration data from another source; withpolymerization reactions, polymer concentration is directly related tomonomer conversion. In the present invention, such data can be obtainedby measuring heat evolved during reaction (see equation III and IV) or,as described below, by measuring the amount of a gaseous reactantconsumed during reaction. The constants in the MHS relation arefunctions of temperature, polymer composition, polymer conformation, andthe quality of the polymer-solvent interaction. The empirical constants,[η_(o)] and α, have been measured for a variety of polymer-solventpairs, and are tabulated in the literature.

Although equations VI and VII can be used to approximate molecularweight, in situ measurements of viscosity in the present invention areused mainly to rank reaction products as a function of molecular weight.Under most circumstances, the amount of solvent necessary to satisfy theconcentration requirement of equation VI would slow the rate of reactionto an unacceptable level. Therefore, most polymerizations are carriedout at polymer concentrations above the semidilute limit, where the useof equations VI and VII to calculate molecular weight would lead tolarge error. Nevertheless, viscosity can be used to rank reactionproducts even at concentrations above the semidilute limit since a risein viscosity during reaction generally reflects an increase in polymerconcentration, molecular weight or both. If necessary, one canaccurately determine molecular weight from viscosity measurements atrelatively high polymer concentration by first preparingtemperature-dependent calibration curves that relate viscosity tomolecular weight. But the curves would have to be obtained for everypolymer-solvent pair produced, which weighs against their use forscreening new polymeric materials.

In addition to ranking reactions, viscosity measurements can also beused to screen or characterize dilute suspensions of insolubleparticles—polymer emulsions or porous supports for heterogeneouscatalysts—in which viscosity increases with particle size at a fixednumber concentration. In the case of polymer emulsions, viscosity canserve as a measure of emulsion quality. For example, solution viscositythat is constant over long periods of time may indicate superioremulsion stability, or viscosity within a particular range may correlatewith a desired emulsion particle size. With porous supports, viscositymeasurements can be used to identify active catalysts: in many cases,the catalyst support will swell during reaction due to the formation ofinsoluble products within the porous support.

In accordance with the present invention, viscosity or relatedproperties of the reactant mixtures are monitored by measuring theeffect of viscous forces on stirring blade rotation. Viscosity is ameasure of a fluid's resistance to a shear force. This shear force isequal to the applied torque, Γ, needed to maintain a constant angularvelocity of the stirring blade. The relationship between the viscosityof the reaction mixture and the applied torque can be expressed as

Γ=K_(ω)(ω,T)η,  VIII

where K_(ω) is a proportionality constant that depends on the angularfrequency, ω, of the stirring bar, the temperature of the reactionmixture, and the geometries of the reaction vessel and the stirringblade. K₁₀₇ can be obtained through calibration with solutions of knownviscosity.

During a polymerization, the viscosity of the reaction mixture increasesover time due to the increase in molecular weight of the reactionproduct or polymer concentration or both. This change in viscosity canbe monitored by measuring the applied torque and using equation VIII toconvert the measured data to viscosity. In many instances, actual valuesfor the viscosity are unnecessary, and one can dispense with theconversion step. For example, in situ measurements of applied torque canbe used to rank reaction products based on molecular weight orconversion, as long as stirring rate, temperature, vessel geometry andstirring blade geometry are about the same for each reaction mixture.

FIG. 23 illustrates an apparatus 700 for directly measuring the appliedtorque. The apparatus 700 comprises a stirring blade 702 coupled to adrive motor 704 via a rigid drive spindle 706. The stirring blade 702 isimmersed in a reaction mixture 708 contained within a reactor vessel710. Upper 712 and lower 714 supports prevent the drive motor 704 andvessel 710 from rotating during operation of the stirring blade 702. Forsimplicity, the lower support 714 can be a permanent magnet. A torque orstrain gauge 716 shown mounted between the upper support 712 and thedrive motor 704 measures the average torque exerted by the motor 704 onthe stirring blade 702. In alternate embodiments, the strain gauge 716is inserted within the drive spindle 706 or is placed between the vessel710 and the lower support 714. If located within the drive spindle 706,a system of brushes or commutators (not shown) are provided to allowcommunication with the rotating strain gauge. Often, placement of thestrain gauge 716 between the vessel 710 and the lower support 714 is thebest option since many stirring systems, such as the one shown in FIG.10, use a single motor to drive multiple stirring blades.

FIG. 24 shows placement of a strain gauge 730 in a portion of a baseplate 732 that is similar to the lower plate 400 of the reactor module390 shown in FIG. 10. The lower end 734 of the strain gauge 730 isrigidly attached to the base plate 732. A first permanent magnet 736 ismounted on the top end 738 of the strain gauge 730, and a secondpermanent magnet 740 is attached to the bottom 742 of a reactor vessel744. When the vessel 744 is inserted in the base plate 732, the magneticcoupling between the first magnet 736 and the second magnet 740 preventsthe vessel 744 from rotating and transmits torque to the strain gauge730.

Besides using a strain gauge, one can also monitor drive motor powerconsumption, which is related to the applied torque. Referring again toFIG. 23, the method requires monitoring and control of the stirringblade 702 rotational speed, which can be accomplished by mounting asensor 718 adjacent to the drive spindle 706. Suitable sensors 718include optical detectors, which register the passage of a spot on thedrive spindle 706 by a reflectance measurement, or which note theinterruption of a light beam by an obstruction mounted on the drivespindle 706, or which discern the passage of a light beam through a sloton the drive spindle 706 or on a co-rotating obstruction. Other suitablesensors 718 include magnetic field detectors that sense the rotation ofa permanent magnet affixed to the spindle 706. Operational details ofmagnetic field sensors are described below in the discussion of phaselag detection. Sensors such as encoders, resolvers, Hall effect sensors,and the like, are commonly integrated into the motor 704. An externalprocessor 720 adjusts the power supplied to the drive motor 704 tomaintain a constant spindle 706 rotational speed. By calibrating therequired power against a series of liquids of known viscosity, theviscosity of an unknown reaction mixture can be determined.

In addition to direct measurement, torque can be determined indirectlyby measuring the phase angle or phase lag between the stirring blade andthe driving force or torque. Indirect measurement requires that thecoupling between the driving torque and the stirring blade is “soft,” sothat significant and measurable phase lag occurs.

With magnetic stirring, “soft” coupling occurs automatically. The torqueon the stirring bar is related to the magnetic moment of the stirringbar, μ, and the amplitude of the magnetic field that drives the rotationof the stirring bar, H, through the expression

Γ=μH sin θ,  IX

where θ is the angle between the axis of the stirring bar (magneticmoment) and the direction of the magnetic field. At a given angularfrequency, and for known μ and H, the phase angle, θ, will automaticallyadjust itself to the value necessary to provide the amount of torqueneeded at that frequency. If the torque required to stir at frequency ωis proportional to the solution viscosity and the stirring frequency—anapproximation useful for discussion—then the viscosity can be calculatedfrom measurements of the phase angle using the equation

Γ=μH sin θ=aηω  X

where a is a proportionality constant that depends on temperature, andthe geometry of the vessel and the stirring blade. In practice, one mayuse equation VIII or a similar empirical expression for the right handside of equation X if the torque does not depend linearly on theviscosity-frequency product.

FIG. 25 shows an inductive sensing coil system 760 for measuring phaseangle or phase lag, θ. The system 760 comprises four electromagnets 762,which drive the magnetic stirring bar 764, and a phase-sensitivedetector, such as a standard lock-in amplifier (not shown). A gradientcoil 766 configuration is used to sense motion of the stirring bar 764,though many other well known inductive sensing coil configurations canbe used. The gradient coil 766 is comprised of a first sensing coil 768and a second sensing coil 770 that are connected in series and arewrapped in opposite directions around a first electromagnet 772. Becauseof their opposite polarities, any difference in voltages induced in thetwo sensing coils 768, 770 will appear as a voltage difference acrossthe terminals 774, which is detected by the lock-in amplifier. If nostirring bar 764 is present, then the alternating magnetic field of thefirst electromagnet 772 will induce approximately equal voltages in eachof the two coils 768, 770—assuming they are mounted symmetrically withrespect to the first electromagnet 772—and the net voltage across theterminals 774 will be about zero. When a magnetic stirring bar 764 ispresent, the motion of the rotating magnet 764 will induce a voltage ineach of the two sensing coils 768, 770. But, the voltage induced in thefirst coil 768, which is closer to the stirring bar 764, will be muchlarger than the voltage induced in the second coil 770, so that thevoltage across the terminals 774 will be nonzero. A periodic signal willthus be induced in the sensing coils 768, 770, which is measured by thelock-in amplifier.

FIG. 26 and FIG. 27 show typical outputs 790, 810 from the inductivesensing coil system 760 of FIG. 25, which illustrate phase lagassociated with magnetic stirring for low and high viscosity solutions,respectively. Periodic signals 792, 812 from the sensing coils 768, 770are plotted with sinusoidal reference signals 794, 814 used to drive theelectromagnets. Time delay, Δt 796, 816, between the periodic signals792, 812 and the reference signals 794, 814 is related to the phaseangle by θ=ω·Δt. Visually comparing the two outputs 790, 810 indicatesthat the phase angle associated with the high viscosity solution islarger than the phase angle associated with the low viscosity solution.

FIG. 27 illustrates how amplitude and phase angle will vary during areaction as the viscosity increases from a low value to a valuesufficient to stall the stirring bar. A waveform or signal 820 from thesensing coils is input to a lock-in amplifier 822, using the drivecircuit sinusoidal current as a phase and frequency reference signal824. The lock-in amplifier 822 outputs the amplitude 826 of the sensingcoil signal 820, and phase angle 828 or phase lag relative to thereference signal 824. The maximum phase angle is {fraction (π/2)}radians, since, as shown by equation X, torque decreases with furtherincreases in θ leading to slip of the stirring bar 764 of FIG. 25. Thus,as viscosity increases during reaction, the phase angle 828 or phase lagalso increases until the stirring bar stalls, and the amplitude 826abruptly drops to zero. This can be seen graphically in FIG. 27, whichshows plots of {overscore (A)} 830 and {overscore (θ)} 832, theamplitude of the reference signal and phase angle, respectively,averaged over many stirring bar rotations. One can optimize thesensitivity of the phase angle 828 measurement by proper choice of themagnetic field amplitude and frequency.

To minimize interference from neighboring stirring bars—ideally, eachset of gradient coils should sense the motion of a single stirringbar—each vessel should be provided with electromagnets that are notshared with adjacent vessels. For example, a 4:1 magnet array shown inFIG. 14 should be used instead of the 2:1 or the 1:1 magnet arrays shownin FIGS. 13 and 12, respectively. In order to take readings from all ofthe vessels in an array, a multiplexer can be used to sequentially routesignals from each vessel to the lock-in amplifier. Normally, an accuratemeasurement of the phase angle can be obtained after several tens ofrotations of the stirring bars. For rotation frequencies of 10-20 Hz,this time will be on the order of a few seconds per vessel. Thus, phaseangle measurements for an entire array of vessels can be typically madeonce every few minutes, depending on the number of vessels, the stirringbar frequency, and the desired accuracy. In order to speed up themeasurement process, one may employ multiple-channel signal detection tomeasure the phase angle of stirring bars in more than one vessel at atime. Alternate detection methods include direct digitization of thecoil output waveforms using a high-speed multiplexer and/or ananalog-to-digital converter, followed by analysis of stored waveforms todetermine amplitude and phase angle.

Phase angle measurements can also be made with non-magnetic, mechanicalstirring drives, using the inductive coil system 760 of FIG. 25. Forexample, one may achieve sufficient phase lag between the stirring bladeand the drive motor by joining them with a torsionally soft, flexibleconnector. Alternatively, the drive mechanism may use a resilient beltdrive rather than a rigid gear drive to produce measurable phase lag.The stirring blade must include a permanent magnet oriented such thatits magnetic moment is not parallel to the axis of rotation. For maximumsensitivity, the magnetic moment of the stirring blade should lie in theplane of rotation. Note that one advantage to using a non-magneticstirring drive is that there is no upper limit on the phase angle.

In addition to directly or indirectly measuring torque, one may senseviscosity by increasing the driving frequency, ω_(D), or decreasing themagnetic field strength until, in either case, the stirring bar stallsbecause of insufficient torque. The point at which the stirring barstops rotating can be detected using the same setup depicted in FIG. 25for measuring phase angle. During a ramp up (down) of the drivingfrequency (field strength), the magnitude of the lock-in amplifieroutput will abruptly fall by a large amount when the stirring barstalls. The frequency or field strength at which the stirring bar stallscan be correlated with viscosity: the lower the frequency or the higherthe field strength at which stalling occurs, the greater the viscosityof the reaction mixture.

With appropriate calibration, the method can yield absolute viscositydata, but generally the method is used to rank reactions. For example,when screening multiple reaction mixtures, one may subject all of thevessels to a series of step changes in either frequency or fieldstrength, while noting which stirring bars stall after each of the stepchanges. The order in which the stirring bars stall indicates therelative viscosity of the reaction mixtures since stirring bars immersedin mixtures having higher viscosity will stall early. Note that, inaddition to providing data on torque and stall frequency, the inductivesensing coil system 760 of FIG. 25 and similar devices can be used asdiagnostic tools to indicate whether a magnetic stirring bar has stoppedrotating during a reaction.

Mechanical Oscillators

Piezoelectric quartz resonators or mechanical oscillators can be used toevaluate the viscosity of reaction mixtures, as well as a host of othermaterial properties, including molecular weight, specific gravity,elasticity, dielectric constant, and conductivity. In a typicalapplication, the mechanical oscillator, which can be as small as a fewmm in length, is immersed in the reaction mixture. The response of theoscillator to an excitation signal is obtained for a range of inputsignal frequencies, and depends on the composition and properties of thereaction mixture. By calibrating the resonator with a set of wellcharacterized liquid standards, the properties of the reaction mixturecan be determined from the response of the mechanical oscillator.Further details on the use of piezoelectric quartz oscillators tomeasure material properties are described in co-pending U.S. patentapplication Ser. No. 09/133,171 “Method and Apparatus for CharacterizingMaterials by Using a Mechanical Resonator,” filed Aug. 12, 1998, whichis herein incorporated by reference.

Although many different kinds of mechanical oscillators currently exist,some are less useful for measuring properties of liquid solutions. Forexample, ultrasonic transducers or oscillators cannot be used in allliquids due to diffraction effects and steady acoustic (compressive)waves generated within the reactor vessel. These effects usually occurwhen the size of the oscillator and the vessel are not much greater thanthe characteristic wavelength of the acoustic waves. Thus, for reactorvessel diameters on the order of a few centimeters, the frequency of themechanical oscillator should be above 1 MHz. Unfortunately, complexliquids and mixtures, including polymer solutions, often behave likeelastic gels at these high frequencies, which results in inaccurateresonator response.

Often, shear-mode transducers as well as various surface-wavetransducers can be used to avoid some of the problems associated withtypical ultrasonic transducers. Because of the manner in which theyvibrate, shear mode transducers generate viscous shear waves instead ofacoustic waves. Since viscous shear waves decay exponentially withdistance from the sensor surface, such sensors tend to be insensitive tothe geometry of the measurement volume, thus eliminating mostdiffraction and reflection problems. Unfortunately, the operatingfrequency of these sensors is also high, which, as mentioned above,restricts their use to simple fluids. Moreover, at high vibrationfrequencies, most of the interaction between the sensor and the fluid isconfined to a thin layer of liquid near the sensor surface. Anymodification of the sensor surface through adsorption of solutioncomponents will often result in dramatic changes in the resonatorresponse.

Tuning forks 840 and bimorph/unimorph resonators 850 shown in FIG. 28and FIG. 29, respectively, overcome many of the drawbacks associatedwith ultrasonic transducers. Because of their small size, tuning forks840 and bimorph/unimorph resonators 850 have difficulty excitingacoustic waves, which typically have wavelengths many times their size.Furthermore, though one might conclude otherwise based on the vibrationmode shown in FIG. 28, tuning forks 840 generate virtually no acousticwaves: when excited, each of the tines 832 of the tuning fork 840 actsas a separate acoustic wave generator, but because the tines 832oscillate in opposite directions and phases, the waves generated by eachof the tines 832 cancel one another. Like the shear mode transducersdescribed above, the bimorph/unimorph 850 resonators producepredominantly viscous waves and therefore tend to be insensitive to thegeometry of the measurement volume. But unlike the shear modetransducers, bimorph/unimorph 850 resonators operate at much lowerfrequencies, and therefore can be used to measure properties ofpolymeric solutions.

FIG. 30 schematically shows a system 870 for measuring the properties ofreaction mixtures using mechanical oscillators 872. An importantadvantage of the system 870 is that it can be used to monitor theprogress of a reaction. The oscillators 872 are mounted on the interiorwalls 874 of the reaction vessels 876. Alternatively, the oscillators872 can be mounted along the bottom 878 of the vessels 876 or can befreestanding within the reaction mixtures 880. Each oscillator 872communicates with a network analyzer 882 (for example, an HP8751Aanalyzer), which generates a variable frequency excitation signal. Eachof the oscillators 872 also serve as receivers, transmitting theirresponse signals back to the network analyzer 882 for processing. Thenetwork analyzer 882 records the responses of the oscillators 872 asfunctions of frequency, and sends the data to storage 884. The outputsignals of the oscillators 872 pass through a high impedance bufferamplifier 886 prior to measurement by the wide band receiver 888 of thenetwork analyzer 882.

Other resonator designs may be used. For example, to improve thesuppression of acoustic waves, a tuning fork resonator with four tinescan be used. It is also possible to excite resonator oscillationsthrough the use of voltage spikes instead of a frequency sweeping ACsource. With voltage spike excitation, decaying free oscillations of theresonator are recorded instead of the frequency response. A variety ofsignal processing techniques well known to those of skill in the art canbe used to distinguish resonator responses.

Alternate embodiments can be described with reference to the parallelreactor system 130 shown in FIG. 2. A single resonator (not shown) isattached to the 3-axis translation system 150. The translation system150, at the direction of the processor 160, places the resonator withina reactor vessel of interest. A reading of resonator response is takenand compared to calibration curves, which relate the response toviscosity, molecular weight, specific gravity, or other properties. Inanother embodiment, a portion of the reaction mixture is withdrawn froma reactor vessel, using, for example, the liquid handling system 146,and is placed in a separate vessel containing a resonator. The responseof the resonator is measured and compared to calibration data. Althoughthe system 870 shown in FIG. 30 is better suited to monitor solutionproperties in situ, the two alternate embodiments can be used aspost-characterization tools and are much simpler to implement.

In addition to mechanical oscillators, other types of sensors can beused to evaluate material properties. For example, interdigitatedelectrodes can be used to measure dielectric properties of the reactionmixtures.

Pressure Control System

Another technique for assessing reaction kinetics is to monitor pressurechanges due to production or consumption of various gases duringreaction. One embodiment of this technique is shown in FIG. 31. Aparallel reactor 910 comprises a group of reactor vessels 912. Agas-tight cap 914 seals each of the vessels 912 and preventsunintentional gas flow to or from the vessels 912. Prior to placement ofthe cap 914, each of the vessels 912 is loaded with liquid reactants,solvents, catalysts, and other condensed-phase reaction components usingthe liquid handling system 146 shown in FIG. 2. Gaseous reactants fromsource 916 are introduced into each of the vessels 912 through a gasinlet 918. Valves 920, which communicate with a controller 922, are usedto fill the reaction vessels 912 with the requisite amount of gaseousreactants prior to reaction. A pressure sensor 924 communicates with thevessel head space—the volume within each of the vessels 912 thatseparates the cap 914 from the liquid components—through a port 926located in the cap 914. The pressure sensors 924 are coupled to aprocessor 928, which manipulates and stores data. During reaction, anychanges in the head space pressure, at constant temperature, reflectchanges in the amount of gas present in the head space. This pressuredata can be used to determine the molar production or consumption rate,r_(i), of a gaseous component since, for an ideal gas at constanttemperature, $\begin{matrix}{r_{i} = {\frac{1}{RT}\frac{p_{i}}{t}}} & {XI}\end{matrix}$

where R is the universal gas constant and p_(i) is the partial pressureof the ith gaseous component. Temperature sensors 930, which communicatewith the processor 928 through monitor 932, provide data that can beused to account for changes in pressure resulting from variations inhead space temperature. The ideal gas law or similar equation of statecan be used to calculate the pressure correction.

In an alternate embodiment, the valves 920 are used to compensate forthe consumption of a gaseous reactant, in a reaction where there is anet loss in moles of gas-phase components. The valves 920 are regulatedby the valve controller 922, which communicates with the processor 928.At the beginning of the reaction, the valves 920 open to allow gas fromthe high pressure source 916 to enter each of the vessels 912. Once thepressure within each of the vessels 912, as read by the sensor 924,reaches a predetermined value, P_(H), the processor 928 closes thevalves 920. As the reaction consumes the source 916 gas, the totalpressure within each of the vessels 912 decreases. Once the pressure ina particular vessel 912 falls below a predetermined value, P_(L), theprocessor 928 opens the valve 920 associated with the particular vessel912, repressurizing it to P_(H). This process—filling each of thevessels 912 with source 916 gas to P_(H), allowing the head spacepressure to drop below P_(L), and then refilling the vessels 912 withsource 916 gas to P_(H)—is usually repeated many times during the courseof the reaction. Furthermore, the total pressure in the head space ofeach of the vessels 912 is continuously monitored and recorded duringthe gas fill-pressure decay cycle.

An analogous method can be used to investigate reactions where there isa net gain of gas-phase components. At the beginning of a reaction, allreaction materials are introduced into the vessels 912 and the valves920 are closed. As the reaction proceeds, gas production results in arise in head space pressure, which sensors 924 and processor 928 monitorand record. Once the pressure within a particular vessel 912 reachesP_(H), the processor 928 directs the controller 922 to open theappropriate valve 920 to depressurize the vessel 912. The valve 920,which is a multi-port valve, vents the gas from the head space throughan exhaust line 934. Once the head space pressure falls below P_(L), theprocessor 928 instructs the controller 922 to close the valve 920. Thetotal pressure is continuously monitored and recorded during the gasrise-vent cycle.

The gas consumption (production) rates can be estimated from the totalpressure data by a variety of methods. For simplicity, these methods aredescribed in terms of a single reactor vessel 912 and valve 920, butthey apply equally well to a parallel reactor 910 comprising multiplevessels 912 and valves 920. One estimate of gas consumption (production)can be made from the slope of the pressure decay (growth) curvesobtained when the valve is closed. These data, after converting totalpressure to partial pressure based on reaction stoichiometry, can beinserted into equation XI to calculate r_(i), the molar consumption(production) rate. A second estimate can be made by assuming that afixed quantity of gas enters (exits) the vessel during each valve cycle.The frequency at which the reactor is repressurized (depressurized) istherefore proportional to the gas consumption (production) rate. Athird, more accurate estimate can be obtained by assuming a known gasflow rate through the valve. Multiplying this value by the time duringwhich the valve remains open yields an estimate for the quantity of gasthat enters or leaves the vessel during a particular cycle. Dividingthis product by the time between the next valve cycle—that is, the timeit takes for the pressure in the vessel head space to fall from P_(H) toP_(L)—yields an average value for the volumetric gas consumption(production) rate for the particular valve cycle. Summing the quantityof gas added during all of the cycles equals the total volume of gasconsumed (produced) during the reaction.

The most accurate results are obtained by directly measuring thequantity of gas that flows through the valve. This can be done by notingthe change in pressure that occurs during the time the valve is open—theideal gas law can be used to convert this change to the volume of gasthat enters or leaves the vessel. Dividing this quantity by the timebetween a particular valve cycle yields an average volumetric gasconsumption (production) rate for that cycle. Summing the volume changesfor each cycle yields the total volume of gas consumed (produced) in thereaction.

In an alternate embodiment shown in FIG. 31, the gas consumption rate isdirectly measured by inserting flow sensors 936 downstream of the valves920 or by replacing the valves 920 with flow sensors 936. The flowsensors 936 allow continuous monitoring of the mass flow rate of gasentering each of the vessels 912 through the gas inlet 918. To ensuremeaningful comparisons between experiments, the pressure of the source916 gas should remain about constant during an experiment. Although theflow sensors 936 eliminate the need for cycling the valves 920, theminimum detectable flow rates of this embodiment are less than thoseemploying pressure cycling. But, the use of flow sensors 936 isgenerally preferred for fast reactions where the reactant flow ratesinto the vessels 912 are greater than the threshold sensitivity of theflow sensors 936.

EXAMPLES

The following examples are intended as illustrative and non-limiting,and represent specific embodiments of the present invention.

Example 1 Calibration of Mechanical Oscillators for Measuring MolecularWeight

Mechanical oscillators were used to characterize reaction mixturescomprising polystyrene and toluene. To relate resonator response to themolecular weight of polystyrene, the system 870 illustrated in FIG. 30was calibrated using polystyrene standards of known molecular weightdissolved in toluene. Each of the standard polystyrene-toluene solutionshad the same concentration, and were run in separate (identical) vesselsusing tuning fork piezoelectric quartz resonators similar to the oneshown in FIG. 28. Frequency response curves for each resonator wererecorded at intervals between about 10 and 30 seconds.

The calibration runs produced a set of resonator responses that could beused to relate the output from the oscillators 872 immersed in reactionmixtures to polystyrene molecular weight. FIG. 32 shows results ofcalibration runs 970 for the polystyrene-toluene solutions. The curvesare plots of oscillator response for polystyrene-toluene solutionscomprising no polystyrene 952, and polystyrene standards having weightaverage molecular weights (M_(w)) of 2.36×10³ 954, 13.7×10³ 956,114.2×10³ 958, and 1.88×10⁶ 960.

FIG. 33 shows a calibration curve 970 obtained by correlating M_(w) ofthe polystyrene standards with the distance between the frequencyresponse curve for toluene 952 and each of the polystyrene solutions954, 956, 958, 960 of FIG. 32. This distance was calculated using theexpression: $\begin{matrix}{{d_{i} = \sqrt{\frac{1}{f_{1} - f_{0}}{\int_{f_{0}}^{f_{1}}{\left( {R_{0} - R_{i}} \right)^{2}\quad {f}}}}},} & {XII}\end{matrix}$

where f₀ and f₁ are the lower and upper frequencies of the responsecurve, respectively; R₀ is the frequency response of the resonator intoluene, and R_(i) is the resonator response in a particularpolystyrene-toluene solution. Given response curves for an unknownpolystyrene-toluene mixture and pure toluene 952 (FIG. 32), the distancebetween the two curves can be determined from equation XII. Theresulting d_(i) can be located along the calibration curve 970 of FIG.33 to determine M_(w) for the unknown polystyrene-toluene solution.

Example 2 Measurement of Gas-Phase Reactant Consumption by PressureMonitoring and Control

FIG. 34 depicts the pressure recorded during solution polymerization ofethylene to polyethylene. The reaction was carried out in an apparatussimilar to that shown in FIG. 31. An ethylene gas source was used tocompensate for ethylene consumed in the reaction. A valve, under controlof a processor, admitted ethylene gas into the reaction vessel when thevessel head space pressure dropped below P_(L)≈16.1 psig due toconsumption of ethylene. During the gas filling portion of the cycle,the valve remained open until the head space pressure exceededP_(H)≈20.3 psig.

FIG. 35 and FIG. 36 show ethylene consumption rate as a function oftime, and the mass of polyethylene formed as a function of ethyleneconsumed, respectively. The average ethylene consumption rate, −r_(c2,k)(atm·min⁻¹), was determined from the expression $\begin{matrix}{{- r_{{C2},k}} = \frac{\left( {P_{H} - P_{L}} \right)_{k}}{\Delta \quad t_{k}}} & {XIII}\end{matrix}$

where subscript k refers to a particular valve cycle, and Δt_(k) is thetime interval between the valve closing during the present cycle and thevalve opening at the beginning of the next cycle. As shown in FIG. 35,the constant ethylene consumption rate at later times results fromcatalyzed polymerization of ethylene. The high ethylene consumption rateearly in the process results primarily from transport of ethylene intothe catalyst solution prior to establishing an equilibrium ethyleneconcentration in the liquid phase. FIG. 36 shows the amount ofpolyethylene produced as a function of the amount of ethylene consumedby reaction. The amount of polyethylene produced was determined byweighing the reaction products, and the amount of ethylene consumed byreaction was estimated by multiplying the constant average consumptionrate by the total reaction time. A linear least-squares fit to thesedata yields a slope which matches the value predicted from the ideal gaslaw and from knowledge of the reaction temperature and the total volumeoccupied by the gas (the product of vessel head space and number ofvalve cycles during the reaction).

Automated, High Pressure Injection System

FIG. 37 shows a perspective view of an eight-vessel reactor module 1000,of the type shown in FIG. 10, which is fitted with an optional fluidinjection system 1002. The fluid injection system 1002 allows additionof liquids or gases to pressurized vessels, which, as described below,allows additional flexibility and alleviates several problems associatedwith pre-loading vessels with catalysts. In addition, the fluidinjection system 1002 improves concurrent analysis of catalysts bypermitting screening reactions to be selectively quenched through theaddition of a catalyst-killing agent (also herein called a catalystpoison). In addition, the fluid injection system 1002 allows for thesequential addition of comonomers to form block copolymers. Althoughliquids (and the ability to inject liquids) are the focus herein, itwill be appreciated by those of skill in the art that the injectionsystem is also useful for gasses and the term fluid is used to encompassboth liquids and gases.

The fluid injection system 1002 helps solve problems concerningliquid-phase catalytic polymerization of a gaseous monomer. When usingthe reactor module 390 shown in FIG. 10 to screen or characterizepolymerization catalysts, each vessel is normally loaded with a catalystand a solvent prior to reaction. After sealing, gaseous monomer isintroduced into each vessel at a specified pressure to initiatepolymerization. As discussed in Example 1, during the early stages ofreaction, the monomer concentration in the solvent increases as gaseousmonomer dissolves in the solvent. Although the monomer eventuallyreaches an equilibrium concentration in the solvent, catalyst behaviormay be affected by the changing monomer concentration prior toequilibrium. Moreover, as the monomer dissolves in the solvent early inthe reaction, additional gaseous monomer is added to maintain thepressure in the vessel headspace. This makes it difficult to distinguishbetween pressure changes in the vessels due to polymerization in theliquid phase and pressure changes due to monomer transport into thesolvent to establish an equilibrium concentration. These analyticaldifficulties can be avoided using the fluid injection system 1002, sincethe catalyst can be introduced into the vessels after the monomer hasattained an equilibrium concentration in the liquid phase.

The fluid injection system 1002 of FIG. 37 also helps solve problemsthat arise when using the reactor module 390 shown in FIG. 10 toinvestigate catalytic co-polymerization of gaseous and liquidco-monomers. Prior to reaction, each vessel is loaded with a catalystand the liquid co-monomer. After sealing the vessels, gaseous co-monomeris introduced into each vessel to initiate co-polymerization. However,because appreciable time may elapse between loading of liquid componentsand contact with the gaseous co-monomer, the catalyst mayhomo-polymerize a significant fraction of the liquid co-monomer. Inaddition, the relative concentration of the co-monomers in theliquid-phase changes during the early stages of reaction as the gaseousco-monomer dissolves in the liquid phase. Both effects lead toanalytical difficulties that can be avoided using the fluid injectionsystem 1002, since catalysts can be introduced into the vessels afterestablishing an equilibrium concentration of the gaseous and liquidco-monomers in the vessels. In this way, the catalyst contacts the twoco-monomers simultaneously.

The liquid injector system 1002 shown in FIG. 37 also allows users toquench reactions at different times by adding a catalyst poison, whichimproves screening of materials exhibiting a broad range of catalyticactivity. When using the reactor module 390 of FIG. 10 to concurrentlyevaluate library members for catalytic performance, the user may havelittle information about the relative activity of library members. Ifevery reaction is allowed to proceed for the same amount of time, themost active catalysts may generate an excessive amount of product, whichcan hinder post reaction analysis and reactor clean up. Conversely, theleast active catalysts may generate an amount of product insufficientfor characterization. By monitoring the amount of product in each of thevessels—through the gaseous monomer uptake measurement, mechanicaloscillators or phase lag measurements, for instance—the user can stop aparticular reaction by injecting the catalyst poison into the vesselsonce a predetermined conversion is achieved. Thus, within the samereactor and in the same experiment, low and high activity catalysts mayundergo reaction for relatively long and short time periods,respectively, with both sets of catalysts generating about the sameamount of product. Furthermore, with the ethylene pressure beingcontrolled, the fluid injection system allows for easier manufacture ofblock copolymers via the addition of comonomer through the injectionport.

Referring again to FIG. 37, the fluid injection system 1002 comprisesfill ports 1004 attached to an injector manifold 1006. An injectoradapter plate 1008, sandwiched between an upper plate 1010 and block1012 of the reactor module 1000, provides conduits for liquid flowbetween the injector manifold 1006 and each of the wells or vessels (notshown) within the block 1012. Chemically inert valves 1014 attached tothe injector manifold 1006 and located along flow paths connecting thefill ports 104 and the conduits within the adapter plate 1008, are usedto establish or prevent fluid communication between the fill ports 1004and the vessels or wells. Normally, the fluid injection system 1002 isaccessed through the fill ports 1004 using a probe 1016, which is partof an automated liquid delivery system such as the robotic materialhandling system 146 shown in FIG. 2. However, liquids can be manuallyinjected into the vessels through the fill ports 1004 using a pipette,syringe, or similar liquid delivery device. Conventional high-pressureliquid chromatography loop injectors can be used as fill ports 1004.Other useful fill ports 1004 are shown in FIG. 38 and FIG. 39.

FIG. 38 shows a cross sectional view of a first embodiment of a fillport 1004′ having an o-ring seal to minimize liquid leaks. The fill port1004′ comprises a generally cylindrical fill port body 1040 having afirst end 1042 and a second end 1044. An axial bore 1046 runs the lengthof the fill port body 1040. An elastomeric o-ring 1048 is seated withinthe axial bore 1046 at a point where there is an abrupt narrowing 1050,and is held in place with a sleeve 1052 that is threaded into the firstend 1042 of the fill port body 1040. The sleeve 1052 has a center hole1054 that is sized to accommodate the widest part of the probe 1016. Thesleeve 1052 is typically made from a chemically resistant plastic, suchas polyethylethylketone (PEEK), polytetrafluoroethylene (PTFE), and thelike, which minimizes damage to the probe 1016 and fill port 1004′during fluid injection. To aid in installation and removal, the fillport 1004′ has a knurled first outer surface 1056 located adjacent tothe first end 1042 of the fill port 1004′, and a threaded second outersurface 1058, located adjacent to the second end 1044 of the fill port1004′.

FIG. 38 also shows the position of the probe 1016 during fluidinjection. Like a conventional pipette, the probe 1016 is a cylindricaltube having an outer diameter (OD) at the point of liquid delivery thatis smaller than the OD over the majority of the probe 1016 length. As aresult, near the probe tip 1060, there is a transition zone 1062 wherethe probe 1016 OD narrows. Because the inner diameter (ID) of theelastic o-ring 1048 is slightly smaller than the OD of the probe tip1060, a liquid-tight seal is formed along the probe transition zone 1060during fluid injection.

FIG. 39 shows a second embodiment of a fill port 1004″. Like the firstembodiment 1004′ shown in FIG. 38, the second embodiment 1004″ comprisesa generally cylindrical fill port body 1040′ having a first end 1042′and a second end 1044′. But instead of an o-ring, the fill port 1004″shown in FIG. 39 employs an insert 1080 having a tapered axial hole 1082that results a light interference fit, and hence a seal, between theprobe tip 1060 and the ID of the tapered axial hole 1082 during fluidinjection. The insert 1080 can be threaded into the first end 1042′ ofthe fill port 1004″. Typically, the insert 1080 is made from achemically resistant material, such as PEEK, PTFE, perfluoro-elastomersand the like, which minimizes damage to the probe 1016 and fill port1004″ during fluid injection. To aid in removal and installation, thefill port′ has a knurled first outer surface 1056′ located adjacent tothe first end 1042′ of the fill port 1004″, and a threaded second outersurface 1058′ located adjacent to the second end 1044′ of the fill port1004″.

FIG. 40 shows a phantom front view of the injector manifold 1006. Theinjector manifold 1006 includes a series of fill port seats 1100 locatedalong a top surface 1102 of the injector manifold 1006. The fill portseats 1100 are dimensioned to receive the second ends 1044, 1044′ of thefill ports 1004′, 1004″ shown in FIG. 38 and FIG. 39. Locating holes1104, which extend through the injector manifold 1006, locate the valves1014 of FIG. 37 along the front of the injector manifold 1006.

FIG. 41 shows a cross sectional view of the injector manifold 1006 alonga first section line 1106 of FIG. 40. The cross section illustrates oneof a group of first flow paths 1130. The first flow paths 1130 extendfrom the fill port seats 1100, through the injector manifold 1006, tovalve inlet seats 1132. Each of the valve inlet seats 1132 isdimensioned to receive an inlet port (not shown) of one of the valves1014 depicted in FIG. 37. The first flow paths 1130 thus provide fluidcommunication between the fill ports 1004 and the valves 1014 of FIG.37.

FIG. 42 shows a cross sectional view of the injector manifold 1006 alonga second section line 1108 of FIG. 40. The cross section illustrates oneof a group of second flow paths 1150. The second flow paths 1150 extendfrom valve outlet seats 1152, through the injector manifold 1006, tomanifold outlets 1154 located along a back surface 1156 of the injectormanifold 1006. Each of the valve outlet seats 1152 is dimensioned toreceive an outlet port (not shown) of one of the valves 1014 depicted inFIG. 37. The manifold outlets 1154 mate with fluid conduits on theinjector adapter plate 1008. Annular grooves 1158, which surround themanifold outlets 1154, are sized to receive o-rings (not shown) thatseal the fluid connection between the manifold outlets 1154 and thefluid conduits on the injector adapter plate 1008. The second flow paths1150 thus provide fluid communication between the valves 1014 and theinjector adapter plate 1008.

FIG. 43 shows a phantom top view of the injector adapter plate 1008,which serves as an interface between the injector manifold 1006 and theblock 1012 of the reactor module 1000 shown in FIG. 37. The injectoradapter plate 1008 comprises holes 1180 that provide access to thevessels and wells within the block 1012. The injector adapter plate 1008also comprises conduits 1182 extending from a front edge 1184 to thebottom surface of the adapter plate 1008. When the adapter plate 1008 isassembled in the reactor module 1000, inlets 1186 of the conduits 1182make fluid connection with the manifold outlets 1154 shown in FIG. 42.

As shown in FIG. 44, which is a cross sectional side view of theinjector adapter plate 1008 along a section line 1188 of FIG. 43, theconduits 1182 terminate on a bottom surface 1210 of the injector plate1008 at conduit outlets 1212. The bottom surface 1210 of the adapterplate 1008 forms an upper surface of each of the wells in the reactormodule 1000 block 1012 of FIG. 37. To ensure that liquid is properlydelivered into the reaction vessels, elongated well injectors, as shownin FIG. 45 and FIG. 48 below, are connected to the conduit outlets 1212.

FIG. 45 shows an embodiment of a well injector 1230. The well injector1230 is a generally tube having a first end 1232 and a second end 1234.The well injector my have any cross sectional shape, such as round orsquare. The well injector 1230 has a threaded outer surface 1236 nearthe first end 1232 so that it can be attached to threaded conduitoutlets 1212 shown in FIG. 44. Flats 1238 located adjacent to thethreaded outer surface 1236 allow a wrench to assist in screwing thefirst end 1232 of the well injector 1230 into the conduit outlets 1212.The length of the well injector 1230 can be varied. For example, thesecond end 1234 of the well injector 1230 may extend into the liquidmixture; alternatively, the second end 1234 of the injector 1230 mayextend a portion of the way into the vessel headspace. Typically, thewell injector 1230 is made from a chemically resistant material, suchPEEK, PTFE, perfluoro-elastomers and the like.

Fluid injection can be understood by referring to FIGS. 46-48. FIG. 46shows a top view of the reactor module 1000, and FIG. 47 and FIG. 48show, respectively, cross sectional side views of the reactor module1000 along first and second section lines 1260, 1262 shown in FIG. 46.Prior to injection of a catalyst or a liquid reagent, the probe 1016,which initially contains a first solvent, withdraws a predeterminedamount of the liquid reagent from a reagent source. Next, the probe 1016withdraws a predetermined amount of a second solvent from a secondsolvent source, resulting in a slug of liquid reagent suspended betweenthe first and second solvents within the probe 1016. Generally, probemanipulations are carried out using a robotic material handling systemof the type shown in FIG. 2, and the second solvent is the same as thefirst solvent. Alternatively, the second solvent may be omitted. Thismethod applies as well to gases.

FIGS. 47 and 48 show the “closed” and “open” states of the valve 1014prior to, and during, fluid injection, respectively. Once the probe 1016contains the requisite amount of liquid reagent and solvents, the probetip 1058 is inserted in the fill port 1004, creating a seal as shown,for example, in FIG. 38 and FIG. 39. The valve 1014 is then opened, andthe second solvent, liquid reagent, and a portion of the first solventare injected into the reactor module 1000 under pressure. From the fillport 1004, the liquid flows into the injector manifold 1006 through oneof the first flow paths 1130 that extend from the fill port seats 1100to the valve inlet seats 1132. The liquid enters the valve 1014 throughan inlet port 1280, flows through a valve flow path 1282, and exits thevalve 1014 through an outlet port 1284. After leaving the valve 1014,the liquid flows through one of the second flow paths 1150 to a manifoldoutlet 1154. From the manifold outlet 1154, the liquid flows through theinjector adapter plate 1008 within one of the fluid conduits 1182, andis injected into a reactor vessel 1286 or well 1288 through the wellinjector 1230. In the embodiment shown in FIG. 48, the second end 1234of the well injector 1230 extends only a fraction of the way into thevessel headspace 1290. In other cases, the second end 1234 may extendinto the reaction mixture 1292.

Fluid injection continues until the slug of liquid reagent is injectedinto the reactor vessel 1286 and the flow path from the fill port 1004to the second end 1234 of the well injector 1230 is filled with thefirst solvent. At that point, the valve 1014 is closed, and the probe1016 is withdrawn from the fill port 1004.

Reactor Vessel Pressure Seal and Magnetic Feed-Through StirringMechanism

FIG. 48 shows a stirring mechanism and associated seals for maintainingabove-ambient pressure in the reactor vessels 1286. The direct-drivestirring mechanism 1310 is similar to the one shown in FIG. 10, andcomprises a gear 1312 attached to a spindle 1314 that rotates a blade orpaddle 1316. A dynamic lip seal 1316, which is secured to the upperplate 1010 prevents gas leaks between the rotating spindle 1314 and theupper plate 1010. When newly installed, the lip seal is capable ofmaintaining pressures of about 100 psig. However, with use, the lip seal1316, like o-rings and other dynamic seals, will gradually develop leaksdue to frictional wear. High service temperatures, chemical andparticulate contamination, and stirring speeds hasten dynamic seal wear.

FIG. 49 shows a cross sectional view of a magnetic feed through 1340stirring mechanism that helps minimize gas leaks associated with dynamicseals. The magnetic feed-through 1340 comprises a gear 1342 that isattached to a magnetic driver assembly 1344 using cap screws 1346 orsimilar fasteners. The magnetic driver assembly 1344 has a cylindricalinner wall 1348 and is rotatably mounted on a rigid cylindrical pressurebarrier 1350 using one or more bearings 1352. The bearings 1352 arelocated within an annular gap 1354 between a narrow head portion 1356 ofthe pressure barrier 1350 and the inner wall 1348 of the magnetic driverassembly 1344. A base portion 1358 of the pressure barrier 1350 isaffixed to the upper plate 1010 of the reactor module 1000 shown in FIG.48 so that the axis of the pressure barrier 1350 is about coincidentwith the centerline of the reactor vessel 1286 or well 1288. Thepressure barrier 1350 has a cylindrical interior surface 1360 that isopen only along the base portion 1358 of the pressure barrier 1350.Thus, the interior surface 1360 of the pressure barrier 1350 and thereactor vessel 1286 or well 1288 define a closed chamber.

As can be seen in FIG. 49, the magnetic feed through 1340 furthercomprises a cylindrical magnetic follower 1362 rotatably mounted withinthe pressure barrier 1350 using first 1364 and second 1366 flangedbearings. The first 1364 and second 1366 flanged bearings are located infirst 1368 and second 1370 annular regions 1368 delimited by theinterior surface 1360 of the pressure barrier 1350 and relatively narrowhead 1372 and leg 1374 portions of the magnetic follower 1362,respectively. A keeper 1376 and retaining clip 1378 located within thesecond annular region 1370 adjacent to the second flanged bearing 1366help minimize axial motion of the magnetic follower 1362. A spindle (notshown) attached to the free end 1380 of the leg 1374 of the magneticfollower 1362, transmits torque to the paddle 1316 immersed in thereaction mixture 1292 shown in FIG. 48.

During operation, the rotating gear 1342 and magnetic driver assembly1344 transmit torque through the rigid pressure barrier 1350 to thecylindrical magnetic follower 1362. Permanent magnets (not shown)embedded in the magnetic driver assembly 1344 have magnet flux vectorsaligned nearly radial to the axis of rotation of the magnetic driverassembly 1344 and follower 1362. These magnets are magnetically coupledto permanent magnets (not shown) that are similarly aligned and embeddedin the magnetic follower 1362. As the drive assembly 1344 is rotated, asmall phase lag is introduced. This phase lag skews the radial magneticflux vectors so a small tangential component is introduced. Thistangential component produces tangential forces on the follower 1362causing a torque about the rotation axis. This torque induces rotationof the follower 1362 and stirring blade or paddle 1316 of FIG. 48. Thefollower 1362 and paddle 1316 rotate at the same frequency as themagnetic driver assembly, though, perhaps, with a measurable phase lag.

Removable and Disposable Stirrer

The stirring mechanism 1310 shown in FIG. 48 includes a multi-piecespindle 1314 comprising an upper spindle portion 1400, a coupler 1402,and a removable stirrer 1404. The multi-piece spindle 1314 offerscertain advantages over a one-piece spindle. Typically, the upper driveshaft 1400 and the coupler 1402 should be made of a high modulusmaterial such as stainless steel, while the removable stirrer 1404 maybe made of a chemically resistant material, such as glass, PEEK, PTFE,perfluoro-elastomers and the like. In contrast, one-piece spindlesgenerally made entirely of high modulus material expensive to fabricateand time-consuming to replace in an assembly, and are therefore normallyreused. Additionally, one-piece spindles are often difficult to cleanafter use, especially following a polymerization reaction. Furthermore,reaction product may be lost during cleaning, which leads to errors incalculating reaction yield. With the multi-piece spindle 1314, onediscards the removable stirrer 1404 after a single use, eliminating thecleaning step. Because the removable stirrer 1404 is easily removed andless bulky than the one-piece spindle, it can be included in certainpost-reaction characterizations, including product weighing to determinereaction yield.

FIG. 50 shows a perspective view of the stirring mechanism 1310 of FIG.48, and provides details of the multi-piece spindle 1314. A gear 1312 isattached to the upper spindle portion 1400 of the multi-piece spindle1314. The upper spindle 1400 passes through a pressure seal assembly1420 containing a dynamic lip seal, and is attached to the removablestirrer 1404 using the coupler 1402. Note that the removable stirrer1404 can also be used with the magnetic feed through stirring mechanism1340 illustrated in FIG. 49. In such cases, the upper spindle 1400 iseliminated and the leg 1374 of the cylindrical magnetic follower 1362 orthe coupler 1402 or both are modified to attach the magnetic follower1362 to the removable stirrer 1404.

FIG. 51 shows details of the coupler 1402, which comprises a cylindricalbody having first 1440 and second 1442 holes centered along an axis ofrotation 1444 of the coupler 1402. The first hole 1440 is dimensioned toreceive a cylindrical end 1446 of the upper spindle 1400. A shoulder1448 formed along the periphery of the upper spindle 1400 rests againstan annular seat 1450 located within the first hole 1440. A set screw(not shown) threaded into a locating hole 1452 prevents relative axialand rotational motion of the upper spindle 1400 and the coupler 1402.

Referring to FIGS. 50 and 51, the second hole 1442 of the coupler 1402is dimensioned to receive a first end 1454 of the removable stirrer1404. A pin 1456, which is embedded in the first end 1454 of theremovable stirrer, cooperates with a locking mechanism 1458 located onthe coupler 1402, to prevent relative rotation of the coupler 1402 andthe removable stirrer 1404. The locking mechanism 1458 comprises anaxial groove 1460 formed in an inner surface 1462 of the coupler. Thegroove 1460 extends from an entrance 1464 of the second hole 1442 to alateral portion 1466 of a slot 1468 cut through a wall 1470 of thecoupler 1402. As shown in FIG. 52, which is a cross sectional view ofthe coupler 1402 along a section line 1472, the lateral portion 1466 ofthe slot 1468 extends about 60 degrees around the circumference of thecoupler 1402 to is an axial portion 1474 of the slot 1468. To connectthe removable stirrer 1404 to the coupler 1402, the first end 1454 ofthe removable stirrer 1404 is inserted into the second hole 1442 andthen rotated so that the pin 1456 travels in the axial groove 1460 andlateral portion 1466 of the slot 1468. A spring 1476, mounted betweenthe coupler 1402 and a shoulder 1478 formed on the periphery of theremovable stirrer 1404, forces the pin 1456 into the axial portion 1474of the slot 1468.

The above description is intended to be illustrative and notrestrictive. Many embodiments as well as many applications besides theexamples provided will be apparent to those of skill in the art uponreading the above description. The scope of the invention shouldtherefore be determined, not with reference to the above description,but should instead be determined with reference to the appended claims,along with the full scope of equivalents to which such claims areentitled. The disclosures of all articles and references, includingpatent applications and publications, are incorporated by reference forall purposes.

What is claimed is:
 1. An apparatus for parallel processing of reactionmixtures comprising: vessels sealed against fluid communication with oneanother and adapted for containing the reaction mixtures at pressuresdifferent than ambient pressures; a stirring system for agitating thereaction mixtures; a temperature control system for regulating thetemperature of the reaction mixtures in the vessels; and an injectionsystem comprising a fluid delivery probe movable from one vessel toanother vessel for effecting the introduction of a fluid into each ofthe vessels at a pressure different than ambient pressure, saidinjection system being operable for preventing leakage of fluid underpressure from each vessel during said introduction by said fluiddelivery probe and after said probe has moved to another vessel.
 2. Theapparatus of claim 1, wherein the injection system comprises: fill portsadapted to receive a fluid delivery probe; first conduits and valves,the first conduits providing fluid communication between the fill portsand the valves; and second conduits and injectors, the second conduitsproviding fluid communication between the valves and the injectors;wherein the injectors are located in the vessels.
 3. The apparatus ofclaim 2, further comprising a robotic handling system, wherein therobotic handling system is adapted to manipulate the fluid deliveryprobe.
 4. The apparatus of claim 3, further comprising a computer tocontrol both the robotic handling system and the valves.
 5. Theapparatus of claim 2, wherein the fill port comprises: an elongated bodyhaving a longitudinal axis and a bore centered on the longitudinal axis,the bore extending the length of the elongated body and characterized byfirst, second, and third diameters, wherein the first diameter isgreater than the second diameter, and the second diameter is greaterthan the third diameter; an elastomeric o-ring seated within the bore ofthe elongated body on a first ledge defined by the second diameter andthe third diameter; and a cylindrical sleeve having a hole centered onits axis of rotation, the hole extending the length of the cylindricalsleeve; wherein the cylindrical sleeve is seated within the bore of theelongated body on a second ledge defined by the first diameter and thesecond diameter and the cylindrical sleeve abuts the elastomeric o-ring.6. The apparatus of claim 5, wherein the cylindrical sleeve is made of achemically resistant plastic material.
 7. The apparatus of claim 6,wherein the chemically resistant plastic material is aperfluoro-elastomer or polyethylethylketone or polytetrafluoroethylene.8. The apparatus of claim 2, wherein the fill port comprises: anelongated body having a longitudinal axis and a bore centered on thelongitudinal axis, the bore extending the length of the elongated bodyand characterized by a first diameter and a second diameter, wherein thefirst diameter is greater than the second diameter; and a cylindricalinsert having a tapered hole centered on its axis of rotation, thetapered hold extending the length of the cylindrical insert; wherein thecylindrical insert is seated within the bore of the elongated body on aledge defined by the first diameter and the second diameter.
 9. Theapparatus of claim 8, wherein the cylindrical insert is made of achemically resistant plastic material.
 10. The apparatus of claim 9,wherein the chemically resistant plastic material is aperfluoro-elastomer or polyethylethylketone or polytetrafluoroethylene.11. The apparatus of claim 2, further comprising a reactor block;wherein the vessels comprise wells formed in the reactor block.
 12. Theapparatus of claim 11, further comprising an injector manifoldassociated with the reactor block and wherein the fill ports and valvesare in fluid communication with the injector manifold.
 13. The apparatusof claim 12, wherein the injector manifold is attached to the reactorblock and the first conduits and the second conduits are passagewaysformed in the injector manifold.
 14. The apparatus of claim 12, whereinthe wells comprise holes extending from a top surface of the reactorblock to a bottom surface of the reactor block, the apparatus furthercomprising: a lower plate disposed on the bottom surface of the reactorblock, the lower plate defining a base of each of the wells; an injectoradapter plate disposed on the top surface of the reactor block, theinjector adapter plate having holes substantially aligned with the wellsand having channels extending from a front edge of the injector adapterplate to a bottom surface of the injector adapter plate, wherein theinjectors are attached to the bottom surface of the injector adapterplate and are in fluid communication with the channels, and the injectormanifold is attached to the front edge of the injector adapter plate sothat the second conduits are in fluid communication with the channels ofthe injector adapter plate; and an upper plate disposed on the injectoradapter plate, the upper plate defining an upper end of each of thewells.
 15. The apparatus of claim 14, wherein the injectors extend intothe reaction mixtures.
 16. Apparatus as set forth in claim 1 whereinsaid injection system further comprises: fill ports for receiving saidprobe, said probe being movable from one fill port to another to deliverfluid; conduits connecting the fill ports and respective vessels; andvalves for opening and closing said conduits, each valve being operableto open to permit the delivery of fluid from the probe to a respectivevessel at a pressure different from ambient pressure, and to close aftersaid delivery.
 17. Apparatus as set forth in claim 16 wherein each fillport is configured for the insertion of said probe therein, saidapparatus further comprising a seal in each fill port for sealingengagement with the probe when the probe is inserted in the fill port.18. Apparatus as set forth in claim 17 wherein said valves are locatedin said conduits downstream from respective fill ports, and wherein eachvalve is operable to close before the probe is completely withdrawn froma respective fill port.
 19. Apparatus as set forth in claim 16 furthercomprising a reactor block having a series of wells therein extendingdown from an upper surface of the block for removably receiving saidvessels therein, and a manifold mounting the fill ports generallyadjacent the upper surface of the reactor block, said conduitscomprising passages in the manifold in fluid communication with saidfill ports for flow of fluid from the probe to said vessels. 20.Apparatus as set forth in claim 19 wherein each fill port comprises abody attached to said manifold, a bore through the body in fluidcommunication with a respective passage in said manifold, and a seal insaid bore adapted for sealing engagement with the probe when the probeis inserted in said bore.
 21. Apparatus as set forth in claim 11 whereinsaid temperature control system is operable to regulate the temperatureof the reaction mixture in each vessel independent of the other vessels.22. An apparatus for parallel processing of reaction mixturescomprising: a reactor block having a series of wells therein extendingdown from an upper surface of the block, an upper plate removablysecured to said reactor block over said upper surface thereof, saidupper plate having openings therein in registry with the wells in thereactor block, removable liners in the wells for containing saidreaction mixtures, a temperature control system for regulating thetemperature of the reaction mixtures; and a stirring system attached tosaid upper plate and removable with the upper plate for agitating thereaction mixtures, the stirring system comprising: spindles extendingdown into respective wells, each of the spindles having a first end anda second end; a stirring blade attached to the first end of each of thespindles; a drive mechanism located external to the vessels that isadapted to rotate the spindles; and magnetic feed through devices formagnetically coupling the drive mechanism to the second end of each ofthe spindles.
 23. The apparatus of claim 22, wherein each of themagnetic feed through devices comprises: a rigid cylindrical pressurebarrier having an interior surface that together with one of the wellsdefines a closed chamber; a magnetic driver rotatably mountedconcentrically with the pressure barrier and external to the closedchamber; and a magnetic follower rotatably mounted within the closedchamber; wherein the drive mechanism is mechanically coupled to rotatethe magnetic driver and the magnetic follower follows the magneticdriver, and the second end of one of the spindles is attached to themagnetic follower so that the spindles rotate as driven by the drivemechanism.
 24. The apparatus of claim 23, wherein the drive mechanismfurther comprises: a motor; and a drive train coupling the motor to themagnetic driver of the magnetic feed through devices.
 25. The apparatusof claim 23, wherein the drive train comprises: gears attached to themotor and to the magnetic driver of the magnetic feed through devices,each of the gears dimensioned and arranged so as to mesh with at leastone adjacent gear so that rotational energy is transmitted along thedrive train from the motor to the spindles through the magnetic feedthrough devices.
 26. An apparatus for parallel processing of reactionmixtures comprising: vessels for containing th e reaction mixtures; atemperature control system for regulating the temperature of thereaction mixtures; and a stirring system for agitating the reactionmixtures, the stirring system comprising multi-piece spindles partiallycontained in the vessels, and a drive mechanism coupled to the spindles,the drive mechanism adapted to rotate the spindles; wherein each of thespindles includes: an upper spindle portion mechanically coupled to thedrive mechanism, and a stirrer of a chemically resistant non-metalmaterial removably attached to the upper spindle portion and containedin one of the vessels.
 27. The apparatus of claim 26, wherein theremovable stirrer is made of plastic.
 28. The apparatus of claim 26,wherein the chemically resistant material is a perfluoro-elastomer orpolyethylethylketone or polytetrafluoroethylene or glass.
 29. Theapparatus of claim 26, further comprising a coupler for reversiblyattaching the removable stirrer to the upper spindle portion, whereinthe coupler comprises: a cylindrical body having first and second holescentered along an axis of rotation of the coupler, the first holedimensioned to receive an end of the upper spindle portion, and thesecond hole of the coupler dimensioned to receive an end of theremovable stirrer.
 30. The apparatus of claim 29, further including alocking mechanism for preventing relative rotation of the coupler andthe removable stirrer comprising: a pin embedded in the end of theremovable stirrer; a spring mounted between the coupler and a shoulderformed on the removable stirrer periphery; and an axial groove extendingfrom an entrance of the second hole to a lateral slot cut through a wallof the coupler, the lateral slot extending partway around the couplercircumference to an axial slot cut through the wall of the coupler;wherein the axial groove, the lateral slot, and the axial slot are sizedto accommodate the pin when the end of the removable stirrer is insertedinto the second hole and rotated, and the pin is held in the axial slotby a force exerted by the spring.
 31. The apparatus of claim 26, whereinthe removable stirrer is snapped into the upper spindle portion.
 32. Amethod of making and characterizing materials comprising the steps of:providing vessels with starting materials to form reaction mixtures;confining the reaction mixture in each vessel against fluidcommunication with the other vessels and at a pressure other thanambient pressure; stirring the reaction mixtures for at least a portionof the confining step; and evaluating the reaction mixtures by trackingat least one characteristic of the reaction for at least a portion ofthe confining step; wherein the confining step further includes a stepof injecting a fluid into at least one of the vessels.
 33. The method ofclaim 32, wherein the fluid of the injecting step comprises a catalyst.34. The method of claim 32, wherein the fluid of the injecting stepcomprises a catalyst poison.
 35. The method of claim 32, wherein thefluid of the injecting step comprises a comonomer.